1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 41, 2023
  5. Article

Annual Review of Immunology

Volume 41, 2023

Immune Mechanisms in Inflammatory Anemia

Abstract

Maintaining the correct number of healthy red blood cells (RBCs) is critical for proper oxygenation of tissues throughout the body. Therefore, RBC homeostasis is a tightly controlled balance between RBC production and RBC clearance, through the processes of erythropoiesis and macrophage hemophagocytosis, respectively. However, during the inflammation associated with infectious, autoimmune, or inflammatory diseases this homeostatic process is often dysregulated, leading to acute or chronic anemia. In each disease setting, multiple mechanisms typically contribute to the development of inflammatory anemia, impinging on both sides of the RBC production and RBC clearance equation. These mechanisms include both direct and indirect effects of inflammatory cytokines and innate sensing. Here, we focus on common innate and adaptive immune mechanisms that contribute to inflammatory anemias using examples from several diseases, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome, severe malarial anemia during infection, and systemic lupus erythematosus, among others.

Keyword(s): anemia, hemophagocyte, hemophagocytic lymphohistiocytosis, inflammation, malaria, sickle cell anemia
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-101320-125839
2023-04-26
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/immunol/41/1/annurev-immunol-101320-125839.html?itemId=/content/journals/10.1146/annurev-immunol-101320-125839&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Chaparro CM, Suchdev PS. 2019. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann. N. Y. Acad. Sci. 1450:115–31
     [Google Scholar]
  2. 2.
    Nairz M, Weiss G. 2020. Iron in infection and immunity. Mol. Aspects Med. 75:100864
     [Google Scholar]
  3. 3.
    Weiss G, Ganz T, Goodnough LT. 2019. Anemia of inflammation. Blood 133:140–50
     [Google Scholar]
  4. 4.
    Schultze JL, Mass E, Schlitzer A. 2019. Emerging principles in myelopoiesis at homeostasis and during infection and inflammation. Immunity 50:2288–301
     [Google Scholar]
  5. 5.
    Doulatov S, Notta F, Laurenti E, Dick JE. 2012. Hematopoiesis: a human perspective. Cell Stem Cell 10:2120–36
     [Google Scholar]
  6. 6.
    Rieger MA, Schroeder T. 2012. Hematopoiesis. Cold Spring Harb. Perspect. Biol. 4:12a008250
     [Google Scholar]
  7. 7.
    Pucella JN, Upadhaya S, Reizis B. 2020. The source and dynamics of adult hematopoiesis: insights from lineage tracing. Annu. Rev. Cell Dev. Biol. 36:529–50
     [Google Scholar]
  8. 8.
    Zivot A, Lipton JM, Narla A, Blanc L. 2018. Erythropoiesis: insights into pathophysiology and treatments in 2017. Mol. Med. 24:111
     [Google Scholar]
  9. 9.
    Neri S, Swinkels DW, Matlung HL, van Bruggen R. 2021. Novel concepts in red blood cell clearance. Curr. Opin. Hematol. 28:6438–44
     [Google Scholar]
  10. 10.
    Oldenborg P-A, Zheleznyak A, Fang Y-F, Lagenaur CF, Gresham HD, Lindberg FP. 2000. Role of CD47 as a marker of self on red blood cells. Science 288:54732051–54
     [Google Scholar]
  11. 11.
    Ha B, Lv Z, Bian Z, Zhang X, Mishra A, Liu Y. 2013.. “ Clustering” SIRPα into the plasma membrane lipid microdomains is required for activated monocytes and macrophages to mediate effective cell surface interactions with CD47. PLOS ONE 8:10e77615
     [Google Scholar]
  12. 12.
    Lv Z, Bian Z, Shi L, Niu S, Ha B et al. 2015. Loss of cell surface CD47 clustering formation and binding avidity to SIRPα facilitate apoptotic cell clearance by macrophages. J. Immunol. 195:2661–71
     [Google Scholar]
  13. 13.
    Grom AA, Horne A, Benedetti FD. 2016. Macrophage activation syndrome in the era of biologic therapy. Nat. Rev. Rheumatol. 12:5259–68
     [Google Scholar]
  14. 14.
    Bracaglia C, Prencipe G, Benedetti FD. 2017. Macrophage Activation Syndrome: different mechanisms leading to a one clinical syndrome. Pediatr. Rheumatol. 15:15
     [Google Scholar]
  15. 15.
    Canna SW, Marsh RA. 2020. Pediatric hemophagocytic lymphohistiocytosis. Blood 135:161332–43
     [Google Scholar]
  16. 16.
    Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D et al. 2011. Hypomorphic mutations in PRF1, MUNC13–4, and STXBP2 are associated with adult-onset familial HLH. Blood 118:225794–98
     [Google Scholar]
  17. 17.
    Schulert GS, Zhang M, Fall N, Husami A, Kissell D et al. 2016. Whole-exome sequencing reveals mutations in genes linked to hemophagocytic lymphohistiocytosis and macrophage activation syndrome in fatal cases of H1N1 influenza. J. Infect. Dis. 213:71180–88
     [Google Scholar]
  18. 18.
    Vastert SJ, van Wijk R, D'Urbano LE, de Vooght KMK, de Jager W et al. 2010. Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis. Rheumatology 49:3441–49
     [Google Scholar]
  19. 19.
    Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C. 2007. Infections associated with haemophagocytic syndrome. Lancet Infect. Dis. 7:12814–22
     [Google Scholar]
  20. 20.
    Henter J, Ehrnst A, Andersson J, Elinder G. 1993. Familial hemophagocytic lymphohistiocytosis and viral infections. Acta Paediatr. 82:4369–72
     [Google Scholar]
  21. 21.
    Jordan MB, Hildeman D, Kappler J, Marrack P. 2004. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 104:3735–43
     [Google Scholar]
  22. 22.
    Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA et al. 2011. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J. Clin. Investig. 121:62264–77
     [Google Scholar]
  23. 23.
    Akilesh HM, Buechler MB, Duggan JM, Hahn WO, Matta B et al. 2019. Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes. Science 363:6423eaao5213
     [Google Scholar]
  24. 24.
    Wang A, Pope SD, Weinstein JS, Yu S, Zhang C et al. 2019. Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice. PNAS 116:62200–9
     [Google Scholar]
  25. 25.
    Strippoli R, Carvello F, Scianaro R, Pasquale LD, Vivarelli M et al. 2012. Amplification of the response to Toll-like receptor ligands by prolonged exposure to interleukin-6 in mice: implication for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatism 64:51680–88
     [Google Scholar]
  26. 26.
    Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B et al. 2014. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat. Genet. 46:101140–46
     [Google Scholar]
  27. 27.
    Romberg N, Moussawi KA, Nelson-Williams C, Stiegler AL, Loring E et al. 2014. Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation. Nat. Genet. 46:101135–39
     [Google Scholar]
  28. 28.
    White NJ. 2018. Anaemia and malaria. Malaria J 17:1371
     [Google Scholar]
  29. 29.
    Tsokos GC. 2020. Autoimmunity and organ damage in systemic lupus erythematosus. Nat. Immunol. 21:6605–14
     [Google Scholar]
  30. 30.
    Giannouli S, Voulgarelis M, Ziakas PD, Tzioufas AG. 2006. Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment. Ann. Rheumatic Diseases 65:2144–48
     [Google Scholar]
  31. 31.
    Elkon KB, Wiedeman A. 2012. Type I IFN system in the development and manifestations of SLE. Curr. Opin. Rheumatol. 24:5499–505
     [Google Scholar]
  32. 32.
    Muskardin TLW, Niewold TB. 2018. Type I interferon in rheumatic diseases. Nat. Rev. Rheumatol. 14:4214–28
     [Google Scholar]
  33. 33.
    Kato GJ, Piel FB, Reid CD, Gaston MH, Ohene-Frempong K et al. 2018. Sickle cell disease. Nat. Rev. Dis. Primers 4:118010
     [Google Scholar]
  34. 34.
    Aidoo M, Terlouw DJ, Kolczak MS, McElroy PD, ter Kuile FO et al. 2002. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet 359:93141311–12
     [Google Scholar]
  35. 35.
    Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. 2013. Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLOS Med. 10:7e1001484
     [Google Scholar]
  36. 36.
    Uyoga S, Olupot-Olupot P, Connon R, Kiguli S, Opoka RO et al. 2022. Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT). Lancet Child Adolesc. Health 6:9606–13
     [Google Scholar]
  37. 37.
    Archer NM, Petersen N, Clark MA, Buckee CO, Childs LM, Duraisingh MT. 2018. Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition. PNAS 115:287350–55
     [Google Scholar]
  38. 38.
    Williams TN, Mwangi TW, Wambua S, Alexander ND, Kortok M et al. 2005. Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. J. Infect. Dis. 192:1178–86
     [Google Scholar]
  39. 39.
    Pagani A, Nai A, Silvestri L, Camaschella C. 2019. Hepcidin and anemia: a tight relationship. Front. Physiol. 10:1294
     [Google Scholar]
  40. 40.
    Wrighting DM, Andrews NC. 2006. Interleukin-6 induces hepcidin expression through STAT3. Blood 108:93204–9
     [Google Scholar]
  41. 41.
    Jelkmann W. 1998. Proinflammatory cytokines lowering erythropoietin production. J. Interf. Cytokine Res. 18:8555–59
     [Google Scholar]
  42. 42.
    Skaar EP. 2010. The battle for iron between bacterial pathogens and their vertebrate hosts. PLOS Pathog 6:8e1000949
     [Google Scholar]
  43. 43.
    Somia IKA, Merati TP, Bakta IM, Manuaba IBP, Yasa WPS et al. 2019. High levels of serum IL-6 and serum hepcidin and low CD4 cell count were risk factors of anemia of chronic disease in HIV patients on the combination of antiretroviral therapy. HIV AIDS 11:133–39
     [Google Scholar]
  44. 44.
    Nai A, Lorè NI, Pagani A, Lorenzo RD, Modica SD et al. 2021. Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients. Am. J. Hematol. 96:1E32–35
     [Google Scholar]
  45. 45.
    Yağcı S, Serin E, Acicbe Ö, Zeren Mİ, Odabaşı MS. 2021. The relationship between serum erythropoietin, hepcidin, and haptoglobin levels with disease severity and other biochemical values in patients with COVID-19. Int. J. Lab. Hematol. 43:Suppl. 1142–51
     [Google Scholar]
  46. 46.
    Bellmann-Weiler R, Lanser L, Barket R, Rangger L, Schapfl A et al. 2020. Prevalence and predictive value of anemia and dysregulated iron homeostasis in patients with COVID-19 infection. J. Clin. Med. 9:82429
     [Google Scholar]
  47. 47.
    Sonnweber T, Boehm A, Sahanic S, Pizzini A, Aichner M et al. 2020. Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study. Respir. Res. 21:1276
     [Google Scholar]
  48. 48.
    Pietras EM, Mirantes-Barbeito C, Fong S, Loeffler D, Kovtonyuk LV et al. 2016. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat. Cell Biol. 18:6607–18
     [Google Scholar]
  49. 49.
    Caiado F, Pietras EM, Manz MG. 2021. Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection. J. Exp. Med. 218:7e20201541
     [Google Scholar]
  50. 50.
    Wolff L, Humeniuk R. 2013. Concise review: erythroid versus myeloid lineage commitment; regulating the master regulators. Stem Cells 31:71237–44
     [Google Scholar]
  51. 51.
    Orozco SL, Canny SP, Hamerman JA. 2021. Signals governing monocyte differentiation during inflammation. Curr. Opin. Immunol. 73:16–24
     [Google Scholar]
  52. 52.
    Etzrodt M, Ahmed N, Hoppe PS, Loeffler D, Skylaki S et al. 2019. Inflammatory signals directly instruct PU.1 in HSCs via TNF. Blood 133:8816–19
     [Google Scholar]
  53. 53.
    Wang C, Xu C-X, Alippe Y, Qu C, Xiao J et al. 2017. Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells. Sci. Rep. 7:14880
     [Google Scholar]
  54. 54.
    Tyrkalska SD, Pérez-Oliva AB, Rodríguez-Ruiz L, Martínez-Morcillo FJ, Alcaraz-Pérez F et al. 2019. Inflammasome regulates hematopoiesis through cleavage of the master erythroid transcription factor GATA1. Immunity 51:150–63.e5
     [Google Scholar]
  55. 55.
    Swann JW, Koneva LA, Regan-Komito D, Sansom SN, Powrie F, Griseri T. 2020. IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors. J. Exp. Med. 217:9e20200164
     [Google Scholar]
  56. 56.
    Broxmeyer HE, Lu L, Platzer E, Feit C, Juliano L, Rubin BY. 1983. Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. J. Immunol. 131:31300–5
     [Google Scholar]
  57. 57.
    Raefsky EL, Platanias LC, Zoumbos NC, Young NS. 1985. Studies of interferon as a regulator of hematopoietic cell proliferation. J. Immunol. 135:42507–12
     [Google Scholar]
  58. 58.
    Wang CQ, Udupa KB, Lipschitz DA. 1995. Interferon-γ exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development. J. Cell. Physiol. 162:1134–38
     [Google Scholar]
  59. 59.
    Dai CH, Price JO, Brunner T, Krantz SB. 1998. Fas ligand is present in human erythroid colony-forming cells and interacts with Fas induced by interferon gamma to produce erythroid cell apoptosis. Blood 91:41235–42
     [Google Scholar]
  60. 60.
    de Bruin AM, Voermans C, Nolte MA. 2014. Impact of interferon-γ on hematopoiesis. Blood 124:162479–86
     [Google Scholar]
  61. 61.
    Libregts SF, Gutiérrez L, de Bruin AM, Wensveen FM, Papadopoulos P et al. 2011. Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. Blood 118:92578–88
     [Google Scholar]
  62. 62.
    Canna SW, Wrobel J, Chu N, Kreiger PA, Paessler M, Behrens EM. 2013. Interferon-γ mediates anemia but is dispensable for fulminant Toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice. Arthritis Rheum. 65:71764–75
     [Google Scholar]
  63. 63.
    Jia J, Zhang Y, Zhang H, Chen Z, Chen L et al. 2022. Hepcidin expression levels involve efficacy of pegylated interferon-α treatment in hepatitis B-infected liver. Int. Immunopharmacol. 107:108641
     [Google Scholar]
  64. 64.
    Ryan JD, Altamura S, Devitt E, Mullins S, Lawless MW et al. 2012. Pegylated interferon-α induced hypoferremia is associated with the immediate response to treatment in hepatitis C. Hepatology 56:2492–500
     [Google Scholar]
  65. 65.
    van Rijnsoever M, Galhenage S, Mollison L, Gummer J, Trengove R, Olynyk JK. 2016. Dysregulated erythropoietin, hepcidin, and bone marrow iron metabolism contribute to interferon-induced anemia in hepatitis C. J. Interferon Cytokine Res. 36:11630–34
     [Google Scholar]
  66. 66.
    Deane JA, Pisitkun P, Barrett RS, Feigenbaum L, Town T et al. 2007. Control of Toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 27:5801–10
     [Google Scholar]
  67. 67.
    Buechler MB, Teal TH, Elkon KB, Hamerman JA. 2013. Cutting edge: Type I IFN drives emergency myelopoiesis and peripheral myeloid expansion during chronic TLR7 signaling. J. Immunol. 190:3886–91
     [Google Scholar]
  68. 68.
    Buechler MB, Akilesh HM, Hamerman JA. 2016. Cutting edge: Direct sensing of TLR7 ligands and type I IFN by the common myeloid progenitor promotes mTOR/PI3K-dependent emergency myelopoiesis. J. Immunol. 197:72577–82
     [Google Scholar]
  69. 69.
    Calandra T, Roger T. 2003. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat. Rev. Immunol. 3:10791–800
     [Google Scholar]
  70. 70.
    Farr L, Ghosh S, Moonah S. 2020. Role of MIF cytokine/CD74 receptor pathway in protecting against injury and promoting repair. Front. Immunol. 11:1273
     [Google Scholar]
  71. 71.
    de Dios Rosado J, Rodriguez-Sosa M. 2011. Macrophage migration inhibitory factor (MIF): a key player in protozoan infections. Int. J. Biol. Sci. 7:91239–56
     [Google Scholar]
  72. 72.
    Martiney JA, Sherry B, Metz CN, Espinoza M, Ferrer AS et al. 2000. Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chabaudi-infected erythrocytes: possible role in the pathogenesis of malarial anemia. Infect. Immun. 68:42259–67
     [Google Scholar]
  73. 73.
    McDevitt MA, Xie J, Ganapathy-Kanniappan S, Shanmugasundaram G, Griffith J et al. 2006. A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia. J. Exp. Med. 203:51185–96. Erratum 2015. J. Exp. Med. 212:5825
     [Google Scholar]
  74. 74.
    Sternberg JM. 2004. Human African trypanosomiasis: clinical presentation and immune response. Parasite Immunol. 26:11–12469–76
     [Google Scholar]
  75. 75.
    Stijlemans B, Leng L, Brys L, Sparkes A, Vansintjan L et al. 2014. MIF contributes to Trypanosoma brucei associated immunopathogenicity development. PLOS Pathog. 10:9e1004414
     [Google Scholar]
  76. 76.
    Stijlemans B, Brys L, Korf H, Bieniasz-Krzywiec P, Sparkes A et al. 2016. MIF-mediated hemodilution promotes pathogenic anemia in experimental African trypanosomosis. PLOS Pathog. 12:9e1005862
     [Google Scholar]
  77. 77.
    Ghosh S, Jiang N, Farr L, Ngobeni R, Moonah S. 2019. Parasite-produced MIF cytokine: role in immune evasion, invasion, and pathogenesis. Front. Immunol. 10:1995
     [Google Scholar]
  78. 78.
    Stosic-Grujicic S, Stojanovic I, Nicoletti F. 2009. MIF in autoimmunity and novel therapeutic approaches. Autoimmun. Rev. 8:3244–49
     [Google Scholar]
  79. 79.
    Jaramillo M, Plante I, Ouellet N, Vandal K, Tessier PA, Olivier M. 2004. Hemozoin-inducible proinflammatory events in vivo: potential role in malaria infection. J. Immunol. 172:53101–10
     [Google Scholar]
  80. 80.
    Banesh S, Layek S, Trivedi V. 2022. Hemin acts as CD36 ligand to activate down-stream signalling to disturb immune responses and cytokine secretion from macrophages. Immunol. Lett. 243:1–18
     [Google Scholar]
  81. 81.
    Thawani N, Tam M, Bellemare M-J, Bohle DS, Olivier M et al. 2014. Plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors. J. Infect. Dis. 209:1140–49
     [Google Scholar]
  82. 82.
    Parroche P, Lauw FN, Goutagny N, Latz E, Monks BG et al. 2007. Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. PNAS 104:61919–24
     [Google Scholar]
  83. 83.
    Gazzinelli RT, Kalantari P, Fitzgerald KA, Golenbock DT. 2014. Innate sensing of malaria parasites. Nat. Rev. Immunol. 14:11744–57
     [Google Scholar]
  84. 84.
    Gowda DC, Wu X. 2018. Parasite recognition and signaling mechanisms in innate immune responses to malaria. Front. Immunol. 9:3006
     [Google Scholar]
  85. 85.
    Köllisch G, Solis FV, Obermann H-L, Eckert J, Müller T et al. 2022. TLR8 is activated by 5′-methylthioinosine, a Plasmodium falciparum-derived intermediate of the purine salvage pathway. Cell Rep. 39:2110691
     [Google Scholar]
  86. 86.
    Luo X-Y, Yang M-H, Peng P, Wu L-J, Liu Q-S et al. 2012. Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia. Lupus 22:2121–27
     [Google Scholar]
  87. 87.
    Tzioufas AG, Kokori SI, Petrovas CI, Moutsopoulos HM. 1997. Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia. Arthritis Rheum. 40:122212–16
     [Google Scholar]
  88. 88.
    Voulgarelis M, Kokori SIG, Ioannidis JPA, Tzioufas AG, Kyriaki D, Moutsopoulos HM. 2000. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin. Ann. Rheum. Dis. 59:3217–22
     [Google Scholar]
  89. 89.
    Schett G, Firbas U, Füreder W, Hiesberger H, Winkler S et al. 2001. Decreased serum erythropoietin and its relation to anti-erythropoietin antibodies in anaemia of systemic lupus erythematosus. Rheumatology 40:4424–31
     [Google Scholar]
  90. 90.
    Hara A, Furuichi K, Yamahana J, Yasuda H, Iwata Y et al. 2016. Effect of autoantibodies to erythropoietin receptor in systemic lupus erythematosus with biopsy-proven lupus nephritis. J. Rheumatol. 43:71328–34
     [Google Scholar]
  91. 91.
    Tsiakalos A, Kordossis T, Ziakas PD, Kontos AN, Kyriaki D, Sipsas NV. 2010. Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related anemia. J. Infection 60:3238–43
     [Google Scholar]
  92. 92.
    Tsiakalos A, Routsias JG, Kordossis T, Moutsopoulos HM, Tzioufas AG, Sipsas NV. 2011. Fine epitope specificity of anti-erythropoietin antibodies reveals molecular mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related anemia. J. Infect. Dis. 204:6902–11
     [Google Scholar]
  93. 93.
    Tsiakalos A, Voumvas T, Psarris A, Oikonomou CK, Ziogas DC et al. 2017. Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia. Hepatobiliary Pancreat. Dis. Int. 16:3289–95
     [Google Scholar]
  94. 94.
    Huang C, Huang C, Yeh M, Hou C, Hou N et al. 2017. Disease severity and erythropoiesis in chronic hepatitis C. J. Gastroenterol. Hepatol. 32:4864–69
     [Google Scholar]
  95. 95.
    Helegbe GK, Huy NT, Yanagi T, Shuaibu MN, Kikuchi M et al. 2013. Anti-erythropoietin antibody levels and its association with anaemia in different strains of semi-immune mice infected with Plasmodium berghei ANKA. Malaria J. 12:1296
     [Google Scholar]
  96. 96.
    Addai-Mensah O, Gyamfi D, Amponsah FA, Annani-Akollor ME, Danquah KO et al. 2019. Anti-erythropoietin antibody production is not associated with malaria and malaria-related anaemia in humans. Sci. World J. 2019:5398732
     [Google Scholar]
  97. 97.
    Theurl I, Hilgendorf I, Nairz M, Tymoszuk P, Haschka D et al. 2016. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat. Med. 22:8945–51
     [Google Scholar]
  98. 98.
    McCullough J. 2014. RBCs as targets of infection. Hematology 2014:1404–9
     [Google Scholar]
  99. 99.
    Ayi K, Lu Z, Serghides L, Ho JM, Finney C et al. 2016. CD47-SIRPα interactions regulate macrophage uptake of Plasmodium falciparum-infected erythrocytes and clearance of malaria in vivo. Infect. Immun. 84:72002–11
     [Google Scholar]
  100. 100.
    Banerjee R, Khandelwal S, Kozakai Y, Sahu B, Kumar S. 2015. CD47 regulates the phagocytic clearance and replication of the Plasmodium yoelii malaria parasite. PNAS 112:103062–67
     [Google Scholar]
  101. 101.
    Isanaka S, Mugusi F, Urassa W, Willett WC, Bosch RJ et al. 2011. Iron deficiency and anemia predict mortality in patients with tuberculosis. J. Nutrition 142:2350–57
     [Google Scholar]
  102. 102.
    Gomes AC, Moreira AC, Silva T, Neves JV, Mesquita G et al. 2019. IFN-γ-dependent reduction of erythrocyte life span leads to anemia during mycobacterial infection. J. Immunol. 203:92485–96
     [Google Scholar]
  103. 103.
    Kidder K, Bian Z, Shi L, Liu Y. 2020. Inflammation unrestrained by SIRPα induces secondary hemophagocytic lymphohistiocytosis independent of IFN-γ. J. Immunol. 205:2821–33
     [Google Scholar]
  104. 104.
    Kuriyama T, Takenaka K, Kohno K, Yamauchi T, Daitoku S et al. 2012. Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis. Blood 120:194058–67
     [Google Scholar]
  105. 105.
    Wu N, Veillette A. 2016. SLAM family receptors in normal immunity and immune pathologies. Curr. Opin. Immunol. 38:45–51
     [Google Scholar]
  106. 106.
    Chen J, Zhong M-C, Guo H, Davidson D, Mishel S et al. 2017. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature 544:7651493–97
     [Google Scholar]
  107. 107.
    Simmons DP, Nguyen HN, Gomez-Rivas E, Jeong Y, Jonsson AH et al. 2022. SLAMF7 engagement superactivates macrophages in acute and chronic inflammation. Sci. Immunol. 7:68eabf2846
     [Google Scholar]
  108. 108.
    Li D, Xiong W, Wang Y, Feng J, He Y et al. 2022. SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. Sci. Immunol. 7:67eabj5501
     [Google Scholar]
  109. 109.
    Bian Z, Shi L, Guo Y-L, Lv Z, Tang C et al. 2016. Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells. PNAS 113:37E5434–43
     [Google Scholar]
  110. 110.
    Ohyagi H, Onai N, Sato T, Yotsumoto S, Liu J et al. 2013. Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. Immunity 39:3584–98
     [Google Scholar]
  111. 111.
    Kuypers FA, Lewis RA, Hua M, Schott MA, Discher D et al. 1996. Detection of altered membrane phospholipid asymmetry in subpopulations of human red blood cells using fluorescently labeled annexin V. Blood 87:31179–87
     [Google Scholar]
  112. 112.
    Wood B, Gibson D, Tait J. 1996. Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations. Blood 88:51873–80
     [Google Scholar]
  113. 113.
    Rivera-Correa J, Rodriguez A. 2018. Divergent roles of antiself antibodies during infection. Trends Immunol. 39:7515–22
     [Google Scholar]
  114. 114.
    Fernandez-Arias C, Rivera-Correa J, Gallego-Delgado J, Rudlaff R, Fernandez C et al. 2016. Anti-self phosphatidylserine antibodies recognize uninfected erythrocytes promoting malarial anemia. Cell Host Microbe 19:2194–203
     [Google Scholar]
  115. 115.
    Rivera-Correa J, Verdi J, Sherman J, Sternberg JM, Raper J, Rodriguez A. 2021. Autoimmunity to phosphatidylserine and anemia in African trypanosome infections. PLOS Negl. Trop. Dis. 15:9e0009814
     [Google Scholar]
  116. 116.
    Bernardoff I, Picq A, Loiseau P, Foret T, Dufrost V et al. 2021. Antiphospholipid antibodies and the risk of autoimmune hemolytic anemia in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun. Rev. 21:1102913
     [Google Scholar]
  117. 117.
    Cao H, Antonopoulos A, Henderson S, Wassall H, Brewin J et al. 2021. Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance. Nat. Commun. 12:11792
     [Google Scholar]
  118. 118.
    Safeukui I, Buffet PA, Deplaine G, Perrot S, Brousse V et al. 2018. Sensing of red blood cells with decreased membrane deformability by the human spleen. Blood Adv. 2:202581–87
     [Google Scholar]
  119. 119.
    Sosale NG, Rouhiparkouhi T, Bradshaw AM, Dimova R, Lipowsky R, Discher DE. 2015. Cell rigidity and shape override CD47’s “self”-signaling in phagocytosis by hyperactivating myosin-II. Blood 125:3542–52
     [Google Scholar]
  120. 120.
    Warncke JD, Beck H-P. 2019. Host cytoskeleton remodeling throughout the blood stages of Plasmodium falciparum. Microbiol. Mol. Biol. Rev. 83:4e00013–19
     [Google Scholar]
  121. 121.
    Safeukui I, Correas J-M, Brousse V, Hirt D, Deplaine G et al. 2008. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood 112:62520–28
     [Google Scholar]
  122. 122.
    Szempruch AJ, Sykes SE, Kieft R, Dennison L, Becker AC et al. 2016. Extracellular vesicles from Trypanosoma brucei mediate virulence factor transfer and cause host anemia. Cell 164:1–2246–57
     [Google Scholar]
  123. 123.
    Hotz MJ, Qing D, Shashaty MGS, Zhang P, Faust H et al. 2018. Red blood cells homeostatically bind mitochondrial DNA through TLR9 to maintain quiescence and to prevent lung injury. Am. J. Respir. Crit. Care Med. 197:4470–80
     [Google Scholar]
  124. 124.
    Lam LKM, Murphy S, Kokkinaki D, Venosa A, Sherrill-Mix S et al. 2021. DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci. Transl. Med. 13:616eabj1008
     [Google Scholar]
  125. 125.
    Nakahira K, Kyung S-Y, Rogers AJ, Gazourian L, Youn S et al. 2013. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLOS Med. 10:12e1001577
     [Google Scholar]
  126. 126.
    Modiano D, Petrarca V, Sirima BS, Nebié I, Diallo D et al. 1996. Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups. PNAS 93:2313206–11
     [Google Scholar]
  127. 127.
    Dolo A, Modiano D, Maiga B, Daou M, Dolo G et al. 2005. Difference in susceptibility to malaria between two sympatric ethnic groups in Mali. Am. J. Trop. Med. Hyg. 72:3243–48
     [Google Scholar]
  128. 128.
    Vafa M, Israelsson E, Maiga B, Dolo A, Doumbo OK, Troye-Blomberg M. 2009. Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. Acta Trop. 109:112–16
     [Google Scholar]
  129. 129.
    Henry B, Volle G, Akpovi H, Gineau L, Roussel C et al. 2022. Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria. EBioMedicine 82:104167
     [Google Scholar]
  130. 130.
    Lindberg FP, Bullard DC, Caver TE, Gresham HD, Beaudet AL, Brown EJ. 1996. Decreased resistance to bacterial infection and granulocyte defects in IAP-deficient mice. Science 274:5288795–98
     [Google Scholar]
  131. 131.
    Subbannayya T, Variar P, Advani J, Nair B, Shankar S et al. 2016. An integrated signal transduction network of macrophage migration inhibitory factor. J. Cell Commun. Signal. 10:2165–70
     [Google Scholar]
  132. 132.
    Benedetti FD, Prencipe G, Bracaglia C, Marasco E, Grom AA. 2021. Targeting interferon-γ in hyperinflammation: opportunities and challenges. Nat. Rev. Rheumatol. 17:11678–91
     [Google Scholar]
  133. 133.
    Henter JI, Elinder G, Söder O, Hansson M, Andersson B, Andersson U. 1991. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 78:112918–22
     [Google Scholar]
  134. 134.
    Bracaglia C, de Graaf K, Marafon DP, Guilhot F, Ferlin W et al. 2017. Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann. Rheum. Dis. 76:1166–72
     [Google Scholar]
  135. 135.
    Put K, Avau A, Brisse E, Mitera T, Put S et al. 2015. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-γ. Rheumatology 54:81507–17
     [Google Scholar]
  136. 136.
    Xu X-J, Tang Y-M, Song H, Yang S-L, Xu W-Q et al. 2012. Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children. J. Pediatrics 160:6984–90.e1
     [Google Scholar]
  137. 137.
    Zoller EE, Lykens JE, Terrell CE, Aliberti J, Filipovich AH et al. 2011. Hemophagocytosis causes a consumptive anemia of inflammation. J. Exp. Med. 208:61203–14
     [Google Scholar]
  138. 138.
    Burn TN, Weaver L, Rood JE, Chu N, Bodansky A et al. 2020. Genetic deficiency of interferon-γ reveals interferon-γ-independent manifestations of murine hemophagocytic lymphohistiocytosis. Arthritis Rheumatol. 72:2335–47
     [Google Scholar]
  139. 139.
    Maschalidi S, Sepulveda FE, Garrigue A, Fischer A, de Saint Basile G. 2016. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood 128:160–71
     [Google Scholar]
  140. 140.
    Brown DE, McCoy MW, Pilonieta MC, Nix RN, Detweiler CS. 2010. Chronic murine typhoid fever is a natural model of secondary hemophagocytic lymphohistiocytosis. PLOS ONE 5:2e9441
     [Google Scholar]
  141. 141.
    Rosche KL, Aljasham AT, Kipfer JN, Piatkowski BT, Konjufca V. 2015. Infection with Salmonella enterica serovar Typhimurium leads to increased proportions of F4/80+ red pulp macrophages and decreased proportions of B and T lymphocytes in the spleen. PLOS ONE 10:6e0130092
     [Google Scholar]
  142. 142.
    Pilonieta MC, Moreland SM, English CN, Detweiler CS. 2014. Salmonella enterica infection stimulates macrophages to hemophagocytose. mBio 5:6e02211
     [Google Scholar]
  143. 143.
    Haldar M, Kohyama M, So AY-L, Kc W, Wu X et al. 2014. Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell 156:61223–34
     [Google Scholar]
  144. 144.
    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 25:113099–109.e3
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-101320-125839
Loading
Immune Mechanisms in Inflammatory Anemia
Annual Review of Immunology 41, 405 (2023); https://doi.org/10.1146/annurev-immunol-101320-125839
/content/journals/10.1146/annurev-immunol-101320-125839
/content/journals/10.1146/annurev-immunol-101320-125839
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error