1932

Abstract

Macrophages and conventional dendritic cells (cDCs) are distributed throughout the body, maintaining tissue homeostasis and tolerance to self and orchestrating innate and adaptive immunity against infection and cancer. As they complement each other, it is important to understand how they cooperate and the mechanisms that integrate their functions. Both are exposed to commensal microbes, pathogens, and other environmental challenges that differ widely among anatomical locations and over time. To adjust to these varying conditions, macrophages and cDCs acquire spatiotemporal adaptations (STAs) at different stages of their life cycle that determine how they respond to infection. The STAs acquired in response to previous infections can result in increased responsiveness to infection, termed training, or in reduced responses, termed paralysis, which in extreme cases can cause immunosuppression. Understanding the developmental stage and location where macrophages and cDCs acquire their STAs, and the molecular and cellular players involved in their induction, may afford opportunities to harness their beneficial outcomes and avoid or reverse their deleterious effects. Here we review our current understanding of macrophage and cDC development, life cycle, function, and STA acquisition before, during, and after infection.We propose a unified framework to explain how these two cell types adjust their activities to changing conditions over space and time to coordinate their immunosurveillance functions.

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2022-04-26
2024-03-28
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Literature Cited

  1. 1. 
    Doherty GJ, McMahon HT. 2009. Mechanisms of endocytosis. Annu. Rev. Biochem. 78:857–902
    [Google Scholar]
  2. 2. 
    Kawai T, Akira S. 2011. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34:637–50
    [Google Scholar]
  3. 3. 
    Chen GY, Nunez G. 2010. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10:826–37
    [Google Scholar]
  4. 4. 
    Iwasaki A, Medzhitov R. 2015. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16:343–53
    [Google Scholar]
  5. 5. 
    Rock KL, Reits E, Neefjes J. 2016. Present yourself! By MHC class I and MHC class II molecules. Trends Immunol 37:724–37
    [Google Scholar]
  6. 6. 
    Segura E, Villadangos JA. 2011. A modular and combinatorial view of the antigen cross-presentation pathway in dendritic cells. Traffic 12:1677–85
    [Google Scholar]
  7. 7. 
    Villadangos JA. 2001. Presentation of antigens by MHC class II molecules: getting the most out of them. Mol. Immunol. 38:329–46
    [Google Scholar]
  8. 8. 
    Villadangos JA, Schnorrer P. 2007. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat. Rev. Immunol. 7:543–55
    [Google Scholar]
  9. 9. 
    Locati M, Curtale G, Mantovani A 2020. Diversity, mechanisms, and significance of macrophage plasticity. Annu. Rev. Pathol. 15:123–47
    [Google Scholar]
  10. 10. 
    Cox N, Pokrovskii M, Vicario R, Geissmann F. 2021. Origins, biology, and diseases of tissue macrophages. Annu. Rev. Immunol. 39:313–44
    [Google Scholar]
  11. 11. 
    Guilliams M, Thierry GR, Bonnardel J, Bajenoff M. 2020. Establishment and maintenance of the macrophage niche. Immunity 52:434–51
    [Google Scholar]
  12. 12. 
    Cabeza-Cabrerizo M, Cardoso A, Minutti CM, Pereira da Costa M, Reis e Sousa C. 2021. Dendritic cells revisited. Annu. Rev. Immunol. 39:131–66
    [Google Scholar]
  13. 13. 
    Pakalniskyte D, Schraml BU. 2017. Tissue-specific diversity and functions of conventional dendritic cells. Adv. Immunol. 134:89–135
    [Google Scholar]
  14. 14. 
    Belkaid Y, Harrison OJ. 2017. Homeostatic immunity and the microbiota. Immunity 46:562–76
    [Google Scholar]
  15. 15. 
    Medzhitov R, Schneider DS, Soares MP. 2012. Disease tolerance as a defense strategy. Science 335:936–41
    [Google Scholar]
  16. 16. 
    Lutz MB, Strobl H, Schuler G, Romani N. 2017. GM-CSF monocyte-derived cells and Langerhans cells as part of the dendritic cell family. Front. Immunol. 8:1388
    [Google Scholar]
  17. 17. 
    Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N et al. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol. 14:571–78
    [Google Scholar]
  18. 18. 
    Reizis B. 2019. Plasmacytoid dendritic cells: development, regulation, and function. Immunity 50:37–50
    [Google Scholar]
  19. 19. 
    Schlitzer A, McGovern N, Ginhoux F. 2015. Dendritic cells and monocyte-derived cells: two complementary and integrated functional systems. Semin. Cell Dev. Biol 41:9–22
    [Google Scholar]
  20. 20. 
    Coillard A, Segura E. 2021. Antigen presentation by mouse monocyte-derived cells: re-evaluating the concept of monocyte-derived dendritic cells. Mol. Immunol. 135:165–69
    [Google Scholar]
  21. 21. 
    Schuler G, Steinman RM. 1985. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med. 161:526–46
    [Google Scholar]
  22. 22. 
    Wilson NS, Villadangos JA. 2004. Lymphoid organ dendritic cells: beyond the Langerhans cells paradigm. Immunol. Cell Biol. 82:91–98
    [Google Scholar]
  23. 23. 
    Romani N, Brunner PM, Stingl G. 2012. Changing views of the role of Langerhans cells. J. Investig. Dermatol. 132:872–81
    [Google Scholar]
  24. 24. 
    Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M et al. 2006. Langerhans cells arise from monocytes in vivo. Nat. Immunol. 7:265–73
    [Google Scholar]
  25. 25. 
    Doebel T, Voisin B, Nagao K. 2017. Langerhans cells—the macrophage in dendritic cell clothing. Trends Immunol 38:817–28
    [Google Scholar]
  26. 26. 
    Sheng J, Chen Q, Wu X, Dong YW, Mayer J, Zhang J et al. 2021. Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population. eLife 10:e65412
    [Google Scholar]
  27. 27. 
    Shek WR. 2008. Role of housing modalities on management and surveillance strategies for adventitious agents of rodents. ILAR J 49:316–25
    [Google Scholar]
  28. 28. 
    Dickson RP, Erb-Downward JR, Falkowski NR, Hunter EM, Ashley SL, Huffnagle GB 2018. The lung microbiota of healthy mice are highly variable, cluster by environment, and reflect variation in baseline lung innate immunity. Am. J. Respir. Crit. Care Med. 198:497–508
    [Google Scholar]
  29. 29. 
    Hamilton SE, Badovinac VP, Beura LK, Pierson M, Jameson SC et al. 2020. New insights into the immune system using dirty mice. J. Immunol. 205:3–11
    [Google Scholar]
  30. 30. 
    Rosshart SP, Vassallo BG, Angeletti D, Hutchinson DS, Morgan AP et al. 2017. Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell 171:1015–28.e13
    [Google Scholar]
  31. 31. 
    Rosshart SP, Herz J, Vassallo BG, Hunter A, Wall MK et al. 2019. Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science 365:eaaw4361
    [Google Scholar]
  32. 32. 
    Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA et al. 2016. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532:51216
    [Google Scholar]
  33. 33. 
    Japp AS, Hoffmann K, Schlickeiser S, Glauben R, Nikolaou C et al. 2017. Wild immunology assessed by multidimensional mass cytometry. Cytometry A 91:85–95
    [Google Scholar]
  34. 34. 
    Ansaldo E, Farley TK, Belkaid Y. 2021. Control of immunity by the microbiota. Annu. Rev. Immunol. 39:449–79
    [Google Scholar]
  35. 35. 
    Masopust D, Sivula CP, Jameson SC. 2017. Of mice, dirty mice, and men: using mice to understand human immunology. J. Immunol. 199:383–88
    [Google Scholar]
  36. 36. 
    Mowat AM, Scott CL, Bain CC. 2017. Barrier-tissue macrophages: functional adaptation to environmental challenges. Nat. Med. 23:1258–70
    [Google Scholar]
  37. 37. 
    Blériot C, Chakarov S, Ginhoux F 2020. Determinants of resident tissue macrophage identity and function. Immunity 52:957–70
    [Google Scholar]
  38. 38. 
    Buechler MB, Fu W, Turley SJ. 2021. Fibroblast-macrophage reciprocal interactions in health, fibrosis, and cancer. Immunity 54:903–15
    [Google Scholar]
  39. 39. 
    Kohyama M, Ise W, Edelson BT, Wilker PR, Hildner K et al. 2009. Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457:318–21
    [Google Scholar]
  40. 40. 
    Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ et al. 2014. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17:131–43
    [Google Scholar]
  41. 41. 
    Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ et al. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159:1327–40
    [Google Scholar]
  42. 42. 
    Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:1312–26
    [Google Scholar]
  43. 43. 
    Okabe Y, Medzhitov R. 2014. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157:832–44
    [Google Scholar]
  44. 44. 
    Schneider C, Nobs SP, Kurrer M, Rehrauer H, Thiele C, Kopf M 2014. Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15:1026–37
    [Google Scholar]
  45. 45. 
    Mass E, Ballesteros I, Farlik M, Halbritter F, Gunther P et al. 2016. Specification of tissue-resident macrophages during organogenesis. Science 353:aaf4238
    [Google Scholar]
  46. 46. 
    Cohen M, Giladi A, Gorki A-D, Solodkin DG, Zada M et al. 2018. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175:1031–44.e18
    [Google Scholar]
  47. 47. 
    Link VM, Duttke SH, Chun HB, Holtman IR, Westin E et al. 2018. Analysis of genetically diverse macrophages reveals local and domain-wide mechanisms that control transcription factor binding and function. Cell 173:1796–809.e17
    [Google Scholar]
  48. 48. 
    Buechler MB, Kim KW, Onufer EJ, Williams JW, Little CC et al. 2019. A stromal niche defined by expression of the transcription factor WT1 mediates programming and homeostasis of cavity-resident macrophages. Immunity 51:119–30.e5
    [Google Scholar]
  49. 49. 
    Camara A, Cordeiro OG, Alloush F, Sponsel J, Chypre M et al. 2019. Lymph node mesenchymal and endothelial stromal cells cooperate via the RANK-RANKL cytokine axis to shape the sinusoidal macrophage niche. Immunity 50:1467–81.e6
    [Google Scholar]
  50. 50. 
    Sakai M, Troutman TD, Seidman JS, Ouyang Z, Spann NJ et al. 2019. Liver-derived signals sequentially reprogram myeloid enhancers to initiate and maintain Kupffer cell identity. Immunity 51:655–70.e8
    [Google Scholar]
  51. 51. 
    Sajti E, Link VM, Ouyang Z, Spann NJ, Westin E et al. 2020. Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung. Nat. Immunol. 21:221–31
    [Google Scholar]
  52. 52. 
    Mulder K, Patel AA, Kong WT, Piot C, Halitzki E et al. 2021. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease. Immunity 54:1883–900.e5
    [Google Scholar]
  53. 53. 
    Evren E, Ringqvist E, Tripathi KP, Sleiers N, Rives IC et al. 2021. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity 54:259–75.e7
    [Google Scholar]
  54. 54. 
    Bain CC, Bravo-Blas A, Scott CL, Perdiguero EG, Geissmann F et al. 2014. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15:929–37
    [Google Scholar]
  55. 55. 
    De Schepper S, Verheijden S, Aguilera-Lizarraga J, Viola MF, Boesmans W et al. 2018. Self-maintaining gut macrophages are essential for intestinal homeostasis. Cell 175:400–15.e13
    [Google Scholar]
  56. 56. 
    Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D et al. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:925–38
    [Google Scholar]
  57. 57. 
    Sere K, Baek JH, Ober-Blobaum J, Muller-Newen G, Tacke F et al. 2012. Two distinct types of Langerhans cells populate the skin during steady state and inflammation. Immunity 37:905–16
    [Google Scholar]
  58. 58. 
    Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB et al. 2013. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38:792–804
    [Google Scholar]
  59. 59. 
    Calderon B, Carrero JA, Ferris ST, Sojka DK, Moore L et al. 2015. The pancreas anatomy conditions the origin and properties of resident macrophages. J. Exp. Med. 212:1497–512
    [Google Scholar]
  60. 60. 
    Ginhoux F, Guilliams M. 2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44:439–49
    [Google Scholar]
  61. 61. 
    van de Laar L, Saelens W, De Prijck S, Martens L, Scott CL et al. 2016. Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44:755–68
    [Google Scholar]
  62. 62. 
    Haldar M, Kohyama M, So AY, Wumesh KC, Wu X et al. 2014. Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell 156:1223–34
    [Google Scholar]
  63. 63. 
    Bonnardel J, T'Jonck W, Gaublomme D, Browaeys R, Scott CL et al. 2019. Stellate cells, hepatocytes, and endothelial cells imprint the Kupffer cell identity on monocytes colonizing the liver macrophage niche. Immunity 51:638–54.e9
    [Google Scholar]
  64. 64. 
    Henson PM. 2017. Cell removal: efferocytosis. Annu. Rev. Cell Dev. Biol. 33:127–44
    [Google Scholar]
  65. 65. 
    Uderhardt S, Martins AJ, Tsang JS, Lämmermann T, Germain RN 2019. Resident macrophages cloak tissue microlesions to prevent neutrophil-driven inflammatory damage. Cell 177:541–55.e17
    [Google Scholar]
  66. 66. 
    Chikina AS, Nadalin F, Maurin M, San-Roman M, Thomas-Bonafos T et al. 2020. Macrophages maintain epithelium integrity by limiting fungal product absorption. Cell 183:411–28.e16
    [Google Scholar]
  67. 67. 
    Vega-Pérez A, Villarrubia LH, Godio C, Gutiérrez-González A, Feo-Lucas L et al. 2021. Resident macrophage-dependent immune cell scaffolds drive anti-bacterial defense in the peritoneal cavity. Immunity 54:2578–94.e5
    [Google Scholar]
  68. 68. 
    Kaufmann SHE, Dorhoi A. 2016. Molecular determinants in phagocyte-bacteria interactions. Immunity 44:476–91
    [Google Scholar]
  69. 69. 
    Ravetch JV, Bolland S. 2001. IgG Fc receptors. Annu. Rev. Immunol. 19:275–90
    [Google Scholar]
  70. 70. 
    van Lookeren Campagne M, Wiesmann C, Brown EJ. 2007. Macrophage complement receptors and pathogen clearance. Cell Microbiol 9:2095–102
    [Google Scholar]
  71. 71. 
    Kuroki Y, Takahashi M, Nishitani C. 2007. Pulmonary collectins in innate immunity of the lung. Cell Microbiol 9:1871–79
    [Google Scholar]
  72. 72. 
    Neupane AS, Willson M, Chojnacki AK, Castanheira FVES, Morehouse C et al. 2020. Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis. Cell 183:110–25.e11
    [Google Scholar]
  73. 73. 
    Roquilly A, Jacqueline C, Davieau M, Molle A, Sadek A et al. 2020. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis. Nat. Immunol. 21:636–48
    [Google Scholar]
  74. 74. 
    Lee J-W, Chun W, Lee HJ, Min J-H, Kim S-M et al. 2021. The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells 10:897
    [Google Scholar]
  75. 75. 
    Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K et al. 2007. Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity 27:240–52
    [Google Scholar]
  76. 76. 
    Abtin A, Jain R, Mitchell AJ, Roediger B, Brzoska AJ et al. 2014. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nat. Immunol. 15:45–53
    [Google Scholar]
  77. 77. 
    Asano K, Takahashi N, Ushiki M, Monya M, Aihara F et al. 2015. Intestinal CD169+ macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes. Nat. Commun. 6:7802
    [Google Scholar]
  78. 78. 
    Goritzka M, Makris S, Kausar F, Durant LR, Pereira C et al. 2015. Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes. J. Exp. Med. 212:699–714
    [Google Scholar]
  79. 79. 
    Bain CC, Scott CL, Uronen-Hansson H, Gudjonsson S, Jansson O et al. 2013. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol 6:498–510
    [Google Scholar]
  80. 80. 
    Snelgrove RJ, Goulding J, Didierlaurent AM, Lyonga D, Vekaria S et al. 2008. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat. Immunol. 9:1074–83
    [Google Scholar]
  81. 81. 
    Janssen WJ, McPhillips KA, Dickinson MG, Linderman DJ, Morimoto K et al. 2008. Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRPα. Am. J. Respir. Crit. Care Med. 178:158–67
    [Google Scholar]
  82. 82. 
    Hussell T, Bell TJ. 2014. Alveolar macrophages: plasticity in a tissue-specific context. Nat. Rev. Immunol. 14:81–93
    [Google Scholar]
  83. 83. 
    Guilliams M, Svedberg FR. 2021. Does tissue imprinting restrict macrophage plasticity?. Nat. Immunol. 22:118–27
    [Google Scholar]
  84. 84. 
    Fanucchi S, Dominguez-Andres J, Joosten LAB, Netea MG, Mhlanga MM. 2021. The intersection of epigenetics and metabolism in trained immunity. Immunity 54:32–43
    [Google Scholar]
  85. 85. 
    Kamath AT, Henri S, Battye F, Tough DF, Shortman K. 2002. Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100:1734–41
    [Google Scholar]
  86. 86. 
    Kamath AT, Pooley J, O'Keeffe MA, Vremec D, Zhan Y et al. 2000. The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J. Immunol. 165:6762–70
    [Google Scholar]
  87. 87. 
    Dress RJ, Wong AY, Ginhoux F. 2018. Homeostatic control of dendritic cell numbers and differentiation. Immunol. Cell Biol. 96:463–76
    [Google Scholar]
  88. 88. 
    Naik SH. 2020. Dendritic cell development at a clonal level within a revised ‘continuous’ model of haematopoiesis. Mol. Immunol. 124:190–97
    [Google Scholar]
  89. 89. 
    Anderson DA 3rd, Dutertre CA, Ginhoux F, Murphy KM 2021. Genetic models of human and mouse dendritic cell development and function. Nat. Rev. Immunol. 21:101–15
    [Google Scholar]
  90. 90. 
    Wilson KR, Villadangos JA, Mintern JD. 2021. Dendritic cell Flt3—regulation, roles and repercussions for immunotherapy. Immunol. Cell Biol. 99:9962–71
    [Google Scholar]
  91. 91. 
    Miller JC, Brown BD, Shay T, Gautier EL, Jojic V et al. 2012. Deciphering the transcriptional network of the dendritic cell lineage. Nat. Immunol. 13:888–99
    [Google Scholar]
  92. 92. 
    Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D et al. 2016. Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Immunity 45:669–84
    [Google Scholar]
  93. 93. 
    Roquilly A, McWilliam HEG, Jacqueline C, Tian Z, Cinotti R et al. 2017. Local modulation of antigen-presenting cell development after resolution of pneumonia induces long-term susceptibility to secondary infections. Immunity 47:135–47.e5
    [Google Scholar]
  94. 94. 
    Rivera CA, Randrian V, Richer W, Gerber-Ferder Y, Delgado MG et al. 2022. Epithelial colonization by gut dendritic cells promotes their functional diversification.. Immunity 55:12944.E8
    [Google Scholar]
  95. 95. 
    Sathe P, Pooley J, Vremec D, Mintern J, Jin JO et al. 2011. The acquisition of antigen cross-presentation function by newly formed dendritic cells. J. Immunol. 186:5184–92
    [Google Scholar]
  96. 96. 
    Acton SE, Farrugia AJ, Astarita JL, Mourao-Sa D, Jenkins RP et al. 2014. Dendritic cells control fibro-blastic reticular network tension and lymph node expansion. Nature 514:498–502
    [Google Scholar]
  97. 97. 
    Kumar V, Dasoveanu DC, Chyou S, Tzeng TC, Rozo C et al. 2015. A dendritic-cell-stromal axis maintains immune responses in lymph nodes. Immunity 42:719–30
    [Google Scholar]
  98. 98. 
    Shortman K. 2020. Dendritic cell development: a personal historical perspective. Mol. Immunol. 119:64–68
    [Google Scholar]
  99. 99. 
    Wilson NS, El-Sukkari D, Villadangos JA. 2004. Dendritic cells constitutively present self antigens in their immature state in vivo, and regulate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood 103:2187–95
    [Google Scholar]
  100. 100. 
    Reis e Sousa C. 2006. Dendritic cells in a mature age. Nat. Rev. Immunol. 6:476–83
    [Google Scholar]
  101. 101. 
    Hammer GE, Ma A. 2013. Molecular control of steady-state dendritic cell maturation and immune homeostasis. Annu. Rev. Immunol. 31:743–91
    [Google Scholar]
  102. 102. 
    Eisenbarth SC. 2019. Dendritic cell subsets in T cell programming: location dictates function. Nat. Rev. Immunol. 19:89–103
    [Google Scholar]
  103. 103. 
    El-Sukkari D, Wilson NS, Hakansson K, Steptoe RJ, Grubb A et al. 2003. The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation. J. Immunol. 171:5003–11
    [Google Scholar]
  104. 104. 
    Wilson NS, El-Sukkari D, Belz GT, Smith CM, Steptoe RJ et al. 2003. Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood 102:2187–94
    [Google Scholar]
  105. 105. 
    den Haan JM, Lehar SM, Bevan MJ. 2000. CD8+ but not CD8 dendritic cells cross-prime cytotoxic T cells in vivo. J. Exp. Med. 192:1685–96
    [Google Scholar]
  106. 106. 
    Iyoda T, Shimoyama S, Liu K, Omatsu Y, Akiyama Y et al. 2002. The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J. Exp. Med. 195:1289–302
    [Google Scholar]
  107. 107. 
    Pooley JL, Heath WR, Shortman K. 2001. Cutting edge: Intravenous soluble antigen is presented to CD4 T cells by CD8 dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells. J. Immunol. 166:5327–30
    [Google Scholar]
  108. 108. 
    Schnorrer P, Behrens GM, Wilson NS, Pooley JL, Smith CM et al. 2006. The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture. PNAS 103:10729–34
    [Google Scholar]
  109. 109. 
    Reuter A, Panozza SE, Macri C, Dumont C, Li J et al. 2015. Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination. J. Immunol. 194:2696–705
    [Google Scholar]
  110. 110. 
    Alloatti A, Kotsias F, Pauwels AM, Carpier JM, Jouve M et al. 2015. Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens. Immunity 43:1087–100
    [Google Scholar]
  111. 111. 
    Cebrian I, Visentin G, Blanchard N, Jouve M, Bobard A et al. 2011. Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells. Cell 147:1355–68
    [Google Scholar]
  112. 112. 
    Guermonprez P, Saveanu L, Kleijmeer M, Davoust J, Van Endert P, Amigorena S. 2003. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 425:397–402
    [Google Scholar]
  113. 113. 
    Houde M, Bertholet S, Gagnon E, Brunet S, Goyette G et al. 2003. Phagosomes are competent organelles for antigen cross-presentation. Nature 425:402–6
    [Google Scholar]
  114. 114. 
    Tullett KM, Tan PS, Park HY, Schittenhelm RB, Michael N et al. 2020. RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells. eLife 9:e63452
    [Google Scholar]
  115. 115. 
    Canton J, Blees H, Henry CM, Buck MD, Schulz O et al. 2021. The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens. Nat. Immunol. 22:140–53
    [Google Scholar]
  116. 116. 
    Blander JM. 2018. Regulation of the cell biology of antigen cross-presentation. Annu. Rev. Immunol. 36:717–53
    [Google Scholar]
  117. 117. 
    Wilson NS, Villadangos JA. 2005. Regulation of antigen presentation and cross-presentation in the dendritic cell network: facts, hypothesis, and immunological implications. Adv. Immunol. 86:241–305
    [Google Scholar]
  118. 118. 
    Liu H, Mintern JD, Villadangos JA. 2019. MARCH ligases in immunity. Curr. Opin. Immunol. 58:38–43
    [Google Scholar]
  119. 119. 
    Schriek P, Liu H, Ching AC, Huang P, Gupta N et al. 2021. Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8. Curr. Res. Immunol. 2:218–28
    [Google Scholar]
  120. 120. 
    Ardouin L, Luche H, Chelbi R, Carpentier S, Shawket A et al. 2016. Broad and largely concordant molecular changes characterize tolerogenic and immunogenic dendritic cell maturation in thymus and periphery. Immunity 45:305–18
    [Google Scholar]
  121. 121. 
    Baratin M, Foray C, Demaria O, Habbeddine M, Pollet E et al. 2015. Homeostatic NF-κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance. Immunity 42:627–39
    [Google Scholar]
  122. 122. 
    Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I et al. 1999. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99:23–33
    [Google Scholar]
  123. 123. 
    Villadangos JA, Schnorrer P, Wilson NS. 2005. Control of MHC class II antigen presentation in dendritic cells: a balance between creative and destructive forces. Immunol. Rev. 207:191–205
    [Google Scholar]
  124. 124. 
    Heath WR, Carbone FR. 2001. Cross-presentation, dendritic cells, tolerance and immunity. Annu. Rev. Immunol. 19:47–64
    [Google Scholar]
  125. 125. 
    Steinman RM, Nussenzweig MC. 2002. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. PNAS 99:351–58
    [Google Scholar]
  126. 126. 
    Walton KL, He J, Kelsall BL, Sartor RB, Fisher NC. 2006. Dendritic cells in germ-free and specific pathogen-free mice have similar phenotypes and in vitro antigen presenting function. Immunol. Lett. 102:16–24
    [Google Scholar]
  127. 127. 
    Wilson NS, Young LJ, Kupresanin F, Naik SH, Vremec D et al. 2008. Normal proportion and expression of maturation markers in migratory dendritic cells in the absence of germs or Toll-like receptor signaling. Immunol. Cell Biol. 86:200–5
    [Google Scholar]
  128. 128. 
    Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J et al. 2007. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27:610–24
    [Google Scholar]
  129. 129. 
    Brand A, Diener N, Zahner SP, Tripp C, Backer RA et al. 2019. E-Cadherin is dispensable to maintain Langerhans cells in the epidermis. J. Investig. Dermatol. 140:132–42
    [Google Scholar]
  130. 130. 
    Hochrein H, O'Keeffe M, Luft T, Vandenabeele S, Grumont RJ et al. 2000. Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. J. Exp. Med. 192:823–33
    [Google Scholar]
  131. 131. 
    Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. 2016. The microbiome and the respiratory tract. Annu. Rev. Physiol. 78:481–504
    [Google Scholar]
  132. 132. 
    Guilliams M, Lambrecht BN, Hammad H. 2013. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol 6:464–73
    [Google Scholar]
  133. 133. 
    Kulikauskaite J, Wack A. 2020. Teaching old dogs new tricks? The plasticity of lung alveolar macrophage subsets. Trends Immunol 41:864–77
    [Google Scholar]
  134. 134. 
    Askenase MH, Han SJ, Byrd AL, Morais da Fonseca D, Bouladoux N et al. 2015. Bone-marrow-resident NK cells prime monocytes for regulatory function during infection. Immunity 42:1130–42
    [Google Scholar]
  135. 135. 
    Lasseaux C, Fourmaux MP, Chamaillard M, Poulin LF. 2017. Type I interferons drive inflammasome-independent emergency monocytopoiesis during endotoxemia. Sci. Rep. 7:16935
    [Google Scholar]
  136. 136. 
    Nahrendorf W, Ivens A, Spence PJ 2021. Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria. eLife 10:e63838
    [Google Scholar]
  137. 137. 
    Boettcher S, Manz MG. 2017. Regulation of inflammation- and infection-driven hematopoiesis. Trends Immunol 38:345–57
    [Google Scholar]
  138. 138. 
    Knapp S, Leemans JC, Florquin S, Branger J, Maris NA et al. 2003. Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. Am. J. Respir. Crit. Care Med. 167:171–79
    [Google Scholar]
  139. 139. 
    Archambaud C, Salcedo SP, Lelouard H, Devilard E, de Bovis B et al. 2010. Contrasting roles of macrophages and dendritic cells in controlling initial pulmonary Brucella infection. Eur. J. Immunol. 40:3458–71
    [Google Scholar]
  140. 140. 
    Schneider C, Nobs SP, Heer AK, Kurrer M, Klinke G et al. 2014. Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLOS Pathog 10:e1004053
    [Google Scholar]
  141. 141. 
    Unanue ER. 1984. Antigen-presenting function of the macrophage. Annu. Rev. Immunol. 2:395–428
    [Google Scholar]
  142. 142. 
    Bosteels C, Neyt K, Vanheerswynghels M, van Helden MJ, Sichien D et al. 2020. Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 52:1039–56.e9
    [Google Scholar]
  143. 143. 
    Yao Y, Jeyanathan M, Haddadi S, Barra NG, Vaseghi-Shanjani M et al. 2018. Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity. Cell 175:1634–50.e17
    [Google Scholar]
  144. 144. 
    Brown AS, Yang C, Fung KY, Bachem A, Bourges D et al. 2016. Cooperation between monocyte-derived cells and lymphoid cells in the acute response to a bacterial lung pathogen. PLOS Pathog 12:e1005691
    [Google Scholar]
  145. 145. 
    Machiels B, Dourcy M, Xiao X, Javaux J, Mesnil C et al. 2017. A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. Nat. Immunol. 18:1310–20
    [Google Scholar]
  146. 146. 
    Aegerter H, Kulikauskaite J, Crotta S, Patel H, Kelly G, Hessel EM et al. 2020. Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection. Nat. Immunol. 21:145–57
    [Google Scholar]
  147. 147. 
    Wijburg OL, Simmons CP, van Rooijen N, Strugnell RA. 2000. Dual role for macrophages in vivo in pathogenesis and control of murine Salmonella enterica var. Typhimurium infections. Eur. J. Immunol. 30:944–53
    [Google Scholar]
  148. 148. 
    Ginhoux F, Bleriot C, Lecuit M. 2017. Dying for a cause: regulated necrosis of tissue-resident macrophages upon infection. Trends Immunol 38:693–95
    [Google Scholar]
  149. 149. 
    Varol C, Mildner A, Jung S 2015. Macrophages: development and tissue specialization. Annu. Rev. Immunol. 33:643–75
    [Google Scholar]
  150. 150. 
    den Haan JM, Kraal G. 2012. Innate immune functions of macrophage subpopulations in the spleen. J. Innate Immun. 4:437–45
    [Google Scholar]
  151. 151. 
    Villadangos JA, Heath WR. 2005. Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm. Semin. Immunol. 17:262–72
    [Google Scholar]
  152. 152. 
    Gupta P, Lai SM, Sheng J, Tetlak P, Balachander A et al. 2016. Tissue-resident CD169+ macrophages form a crucial front line against Plasmodium infection. Cell Rep 16:1749–61
    [Google Scholar]
  153. 153. 
    Carrasco YR, Batista FD. 2007. B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27:160–71
    [Google Scholar]
  154. 154. 
    Miyake Y, Asano K, Kaise H, Uemura M, Nakayama M, Tanaka M. 2007. Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. J. Clin. Investig. 117:2268–78
    [Google Scholar]
  155. 155. 
    Phan TG, Green JA, Gray EE, Xu Y, Cyster JG. 2009. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat. Immunol. 10:786–93
    [Google Scholar]
  156. 156. 
    Backer R, Schwandt T, Greuter M, Oosting M, Jungerkes F et al. 2010. Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. PNAS 107:216–21
    [Google Scholar]
  157. 157. 
    Bellomo A, Gentek R, Bajenoff M, Baratin M. 2018. Lymph node macrophages: scavengers, immune sentinels and trophic effectors. Cell Immunol 330:168–74
    [Google Scholar]
  158. 158. 
    Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN et al. 2005. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308:1626–29
    [Google Scholar]
  159. 159. 
    Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A et al. 2011. CD8α+ dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 35:249–59
    [Google Scholar]
  160. 160. 
    Zhang S, Coughlan HD, Ashayeripanah M, Seizova S, Kueh AJ et al. 2021. Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT. Sci. Immunol. 6:eabf4432
    [Google Scholar]
  161. 161. 
    Broquet A, Roquilly A, Jacqueline C, Potel G, Caillon J, Asehnoune K 2014. Depletion of natural killer cells increases mice susceptibility in a Pseudomonas aeruginosa pneumonia model. Crit. Care Med. 42:e441–50
    [Google Scholar]
  162. 162. 
    Cabeza-Cabrerizo M, van Blijswijk J, Wienert S, Heim D, Jenkins RP et al. 2019. Tissue clonality of dendritic cell subsets and emergency DCpoiesis revealed by multicolor fate mapping of DC progenitors. Sci. Immunol. 4:eaaw1941
    [Google Scholar]
  163. 163. 
    Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H et al. 2013. Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat. Med. 19:730–38
    [Google Scholar]
  164. 164. 
    Bieber K, Autenrieth SE. 2020. Dendritic cell development in infection. Mol. Immunol. 121:111–17
    [Google Scholar]
  165. 165. 
    Helft J, Bottcher J, Chakravarty P, Zelenay S, Huotari J et al. 2015. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity 42:1197–211
    [Google Scholar]
  166. 166. 
    Naik SH, Proietto AI, Wilson NS, Dakic A, Schnorrer P et al. 2005. Cutting edge: generation of splenic CD8+ and CD8 dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J. Immunol. 174:6592–97
    [Google Scholar]
  167. 167. 
    Segura E, Albiston AL, Wicks IP, Chai SY, Villadangos JA. 2009. Different cross-presentation pathways in steady-state and inflammatory dendritic cells. PNAS 106:20377–81
    [Google Scholar]
  168. 168. 
    Gil-Torregrosa BC, Lennon-Dumenil AM, Kessler B, Guermonprez P, Ploegh HL et al. 2004. Control of cross-presentation during dendritic cell maturation. Eur. J. Immunol. 34:398–407
    [Google Scholar]
  169. 169. 
    West MA, Wallin RP, Matthews SP, Svensson HG, Zaru R et al. 2004. Enhanced dendritic cell antigen capture via Toll-like receptor-induced actin remodeling. Science 305:1153–57
    [Google Scholar]
  170. 170. 
    Calmette J, Bertrand M, Vetillard M, Ellouze M, Flint S et al. 2016. Glucocorticoid-induced leucine zipper protein controls macropinocytosis in dendritic cells. J. Immunol. 197:4247–56
    [Google Scholar]
  171. 171. 
    Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, Galan JE, Mellman I. 2000. Developmental control of endocytosis in dendritic cells by Cdc42. Cell 102:325–34
    [Google Scholar]
  172. 172. 
    West MA, Prescott AR, Eskelinen EL, Ridley AJ, Watts C. 2000. Rac is required for constitutive macropinocytosis by dendritic cells but does not control its downregulation. Curr. Biol. 10:839–48
    [Google Scholar]
  173. 173. 
    Wilson NS, Behrens GM, Lundie RJ, Smith CM, Waithman J et al. 2006. Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. Nat. Immunol. 7:165–72
    [Google Scholar]
  174. 174. 
    Alloatti A, Kotsias F, Magalhaes JG, Amigorena S. 2016. Dendritic cell maturation and cross-presentation: Timing matters!. Immunol. Rev. 272:97–108
    [Google Scholar]
  175. 175. 
    Young LJ, Wilson NS, Schnorrer P, Mount A, Lundie RJ et al. 2007. Dendritic cell preactivation impairs MHC class II presentation of vaccines and endogenous viral antigens. PNAS 104:17753–58
    [Google Scholar]
  176. 176. 
    Young LJ, Wilson NS, Schnorrer P, Proietto A, ten Broeke T et al. 2008. Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat. Immunol. 9:1244–52
    [Google Scholar]
  177. 177. 
    Sutherland RM, Londrigan SL, Brady JL, Azher H, Carrington EM et al. 2012. Shutdown of immunological priming and presentation after in vivo administration of adenovirus. Gene Therapy 19:1095–100
    [Google Scholar]
  178. 178. 
    Vega-Ramos J, Roquilly A, Asehnoune K, Villadangos JA 2014. Modulation of dendritic cell antigen presentation by pathogens, tissue damage and secondary inflammatory signals. Curr. Opin. Pharmacol. 17:64–70
    [Google Scholar]
  179. 179. 
    Kampgen E, Koch N, Koch F, Stoger P, Heufler C et al. 1991. Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. PNAS 88:3014–18
    [Google Scholar]
  180. 180. 
    Villadangos JA, Cardoso M, Steptoe RJ, van Berkel D, Pooley J et al. 2001. MHC class II expression is regulated in dendritic cells independently of invariant chain degradation. Immunity 14:739–49
    [Google Scholar]
  181. 181. 
    Simmons DP, Wearsch PA, Canaday DH, Meyerson HJ, Liu YC et al. 2012. Type I IFN drives a distinctive dendritic cell maturation phenotype that allows continued class II MHC synthesis and antigen processing. J. Immunol. 188:3116–26
    [Google Scholar]
  182. 182. 
    Matsuki Y, Ohmura-Hoshino M, Goto E, Aoki M, Mito-Yoshida M et al. 2007. Novel regulation of MHC class II function in B cells. EMBO J 26:846–54
    [Google Scholar]
  183. 183. 
    Joffre O, Nolte MA, Sporri R, Reis e Sousa C. 2009. Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol. Rev. 227:234–47
    [Google Scholar]
  184. 184. 
    Sporri R, Reis e Sousa C. 2005. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat. Immunol. 6:163–70
    [Google Scholar]
  185. 185. 
    Vega-Ramos J, Roquilly A, Zhan Y, Young LJ, Mintern JD, Villadangos JA. 2014. Inflammation conditions mature dendritic cells to retain the capacity to present new antigens but with altered cytokine secretion function. J. Immunol. 193:3851–59
    [Google Scholar]
  186. 186. 
    den Haan JM, Bevan MJ. 2002. Constitutive versus activation-dependent cross-presentation of immune complexes by CD8+ and CD8 dendritic cells in vivo. J. Exp. Med. 196:817–27
    [Google Scholar]
  187. 187. 
    Abdi K, Singh NJ, Matzinger P. 2012. Lipopolysaccharide-activated dendritic cells: “exhausted” or alert and waiting?. J. Immunol. 188:5981–89
    [Google Scholar]
  188. 188. 
    Blecher-Gonen R, Bost P, Hilligan KL, David E, Salame TM et al. 2019. Single-cell analysis of diverse pathogen responses defines a molecular roadmap for generating antigen-specific immunity. Cell Syst 8:109–21.e6
    [Google Scholar]
  189. 189. 
    Miller MA, Ganesan AP, Luckashenak N, Mendonca M, Eisenlohr LC. 2015. Endogenous antigen processing drives the primary CD4+ T cell response to influenza. Nat. Med. 21:1216–22
    [Google Scholar]
  190. 190. 
    van de Weijer ML, Luteijn RD, Wiertz EJ. 2015. Viral immune evasion: lessons in MHC class I antigen presentation. Semin. Immunol. 27:125–37
    [Google Scholar]
  191. 191. 
    Neefjes J, Jongsma ML, Paul P, Bakke O 2011. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol. 11:823–36
    [Google Scholar]
  192. 192. 
    Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA et al. 2006. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25:153–62
    [Google Scholar]
  193. 193. 
    Lundie RJ, de Koning-Ward TF, Davey GM, Nie CQ, Hansen DS et al. 2008. Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α+ dendritic cells. PNAS 105:14509–14
    [Google Scholar]
  194. 194. 
    Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C et al. 2007. Differential antigen processing by dendritic cell subsets in vivo. Science 315:107–11
    [Google Scholar]
  195. 195. 
    Qi H, Egen JG, Huang AY, Germain RN. 2006. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312:1672–76
    [Google Scholar]
  196. 196. 
    Kato Y, Steiner TM, Park HY, Hitchcock RO, Zaid A et al. 2020. Display of native antigen on cDC1 that have spatial access to both T and B cells underlies efficient humoral vaccination. J. Immunol. 205:1842–56
    [Google Scholar]
  197. 197. 
    Heath WR, Kato Y, Steiner TM, Caminschi I. 2019. Antigen presentation by dendritic cells for B cell activation. Curr. Opin. Immunol. 58:44–52
    [Google Scholar]
  198. 198. 
    Schriek P, Ching AC, Moily NS, Moffat J, Beattie L et al. 2022. Marginal zone B cells acquire dendritic cell functions by trogocytosis. Science 375:eabf7470
    [Google Scholar]
  199. 199. 
    Divangahi M, Aaby P, Khader SA, Barreiro LB, Bekkering S et al. 2021. Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat. Immunol. 22:2–6 Erratum. 2021. Nat. Immunol. 22(7):928
    [Google Scholar]
  200. 200. 
    Bekkering S, Dominguez-Andres J, Joosten LAB, Riksen NP, Netea MG. 2021. Trained immunity: reprogramming innate immunity in health and disease. Annu. Rev. Immunol. 39:667–93
    [Google Scholar]
  201. 201. 
    Roquilly A, Villadangos JA. 2015. The role of dendritic cell alterations in susceptibility to hospital-acquired infections during critical-illness related immunosuppression. Mol. Immunol. 68:120–23
    [Google Scholar]
  202. 202. 
    Singh AK, Netea MG, Bishai WR. 2021. BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases. J. Clin. Investig. 131:e148291
    [Google Scholar]
  203. 203. 
    Hotchkiss RS, Monneret G, Payen D. 2013. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol. 13:862–74
    [Google Scholar]
  204. 204. 
    Van der Poll T, Shankar-Hari M, Wiersinga WJ 2021. The immunology of sepsis. Immunity 54:2450–64
    [Google Scholar]
  205. 205. 
    Foster SL, Hargreaves DC, Medzhitov R. 2007. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447:972–78
    [Google Scholar]
  206. 206. 
    Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC et al. 2012. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12:223–32
    [Google Scholar]
  207. 207. 
    Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC et al. 2012. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. PNAS 109:17537–42
    [Google Scholar]
  208. 208. 
    Leopold Wager CM, Hole CR, Campuzano A, Castro-Lopez N, Cai H et al. 2018. IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans. PLOS Pathog 14:e1007358
    [Google Scholar]
  209. 209. 
    Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L et al. 2008. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J. Exp. Med. 205:323–29
    [Google Scholar]
  210. 210. 
    Khan N, Downey J, Sanz J, Kaufmann E, Blankenhaus B et al. 2020. M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity. Cell 183:752–70.e22
    [Google Scholar]
  211. 211. 
    Lundie RJ, Young LJ, Davey GM, Villadangos JA, Carbone FR et al. 2010. Blood-stage Plasmodium berghei infection leads to short-lived parasite-associated antigen presentation by dendritic cells. Eur. J. Immunol. 40:1674–81
    [Google Scholar]
  212. 212. 
    Lai SM, Sheng J, Gupta P, Renia L, Duan K et al. 2018. Organ-specific fate, recruitment, and refilling dynamics of tissue-resident macrophages during blood-stage malaria. Cell Rep 25:3099–109.e3
    [Google Scholar]
  213. 213. 
    Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonca LE et al. 2018. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172:176–90.e19
    [Google Scholar]
  214. 214. 
    Mitroulis I, Ruppova K, Wang B, Chen LS, Grzybek M et al. 2018. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172:147–61.e12
    [Google Scholar]
  215. 215. 
    Villar J, Segura E. 2020. Recent advances towards deciphering human dendritic cell development. Mol. Immunol. 122:109–15
    [Google Scholar]
  216. 216. 
    Szabo PA, Dogra P, Gray JI, Wells SB, Connors TJ et al. 2021. Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity 54:797–814
    [Google Scholar]
  217. 217. 
    Segura E, Durand M, Amigorena S 2013. Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells. J. Exp. Med. 210:1035–47
    [Google Scholar]
  218. 218. 
    Haspeslagh E, Heyndrickx I, Hammad H, Lambrecht BN 2018. The hygiene hypothesis: immunological mechanisms of airway tolerance. Curr. Opin. Immunol. 54:102–8
    [Google Scholar]
  219. 219. 
    Strachan DP. 1989. Hay fever, hygiene, and household size. Br. Med. J. 299:1259–60
    [Google Scholar]
  220. 220. 
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP et al. 2018. Innate lymphoid cells: 10 years on. Cell 174:1054–66
    [Google Scholar]
  221. 221. 
    Mueller SN, Gebhardt T, Carbone FR, Heath WR. 2013. Memory T cell subsets, migration patterns, and tissue residence. Annu. Rev. Immunol. 31:137–61
    [Google Scholar]
  222. 222. 
    Huang L, Yao Q, Gu X, Wang Q, Ren L et al. 2021. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet 398:10302747–58
    [Google Scholar]
  223. 223. 
    Wu X, Liu X, Zhou Y, Yu H, Li R et al. 2021. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Respir. Med. 9:7747–54
    [Google Scholar]
  224. 224. 
    Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L et al. 2020. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 323:161574–81
    [Google Scholar]
  225. 225. 
    Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A et al. 2020. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. New Engl. J. Med. 383:2603–15
    [Google Scholar]
  226. 226. 
    Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT et al. 2021. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19. JAMA 326:6499–518
    [Google Scholar]
  227. 227. 
    Horby P, Lim WS, Emberson JR, Mafham M, Bell JLet al(RECOVERY Collab. Group) 2020. Dexamethasone in hospitalized patients with Covid-19. New Engl. J. Med. 384:8693–704
    [Google Scholar]
  228. 228. 
    Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR et al. 2021. Baricitinib plus remdesivir for hospitalized adults with Covid-19. New Engl. J. Med. 384:9795–807
    [Google Scholar]
  229. 229. 
    Merad M, Martin JC. 2020. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20:6355–62
    [Google Scholar]
  230. 230. 
    Kreutmair S, Unger S, Núñez NG, Ingelfinger F, Alberti C et al. 2021. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia. Immunity 54:71578–93.e5
    [Google Scholar]
  231. 231. 
    Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ et al. 2020. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. 26:71070–76
    [Google Scholar]
  232. 232. 
    Liao M, Liu Y, Yuan J, Wen Y, Xu G et al. 2020. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med. 26:6842–44
    [Google Scholar]
  233. 233. 
    Bouras M, Asehnoune K, Roquilly A 2018. Contribution of dendritic cell responses to sepsis-induced immunosuppression and to susceptibility to secondary pneumonia. Front. Immunol. 9:2590
    [Google Scholar]
  234. 234. 
    Roquilly A, Torres A, Villadangos JA, Netea MG, Dickson R et al. 2019. Pathophysiological role of respiratory dysbiosis in hospital-acquired pneumonia. Lancet Respir. Med. 7:8710–20
    [Google Scholar]
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