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Annual Review of Pathology: Mechanisms of Disease

Volume 19, 2024

Dynamic Multiplex Tissue Imaging in Inflammation Research

Abstract

Inflammation is a highly dynamic process with immune cells that continuously interact with each other and parenchymal components as they migrate through tissue. The dynamic cellular responses and interaction patterns are a function of the complex tissue environment that cannot be fully reconstructed ex vivo, making it necessary to assess cell dynamics and changing spatial patterning in vivo. These dynamics often play out deep within tissues, requiring the optical focus to be placed far below the surface of an opaque organ. With the emergence of commercially available two-photon excitation lasers that can be combined with existing imaging systems, new avenues for imaging deep tissues over long periods of time have become available. We discuss a selected subset of studies illustrating how two-photon microscopy (2PM) has helped to relate the dynamics of immune cells to their in situ function and to understand the molecular patterns that govern their behavior in vivo. We also review some key practical aspects of 2PM methods and point out issues that can confound the results, so that readers can better evaluate the reliability of conclusions drawn using this technology.

Keyword(s): dynamic imaging, intravital imaging, multiplex imaging, tissue imaging, two-photon microscopy
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/content/journals/10.1146/annurev-pathmechdis-070323-124158
2024-01-24
2024-05-05
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Literature Cited

  1. 1.
    Honda T, Egen JG, Lämmermann T, Kastenmüller W, Torabi-Parizi P, Germain RN. 2014. Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues. Immunity 40:2235–47
     [Google Scholar]
  2. 2.
    Heymann F, Niemietz PM, Peusquens J, Ergen C, Kohlhepp M et al. 2015. Long term intravital multiphoton microscopy imaging of immune cells in healthy and diseased liver using CXCR6.Gfp reporter mice. J. Vis. Exp. 97:e52607
     [Google Scholar]
  3. 3.
    von Brühl M-L, Stark K, Steinhart A, Chandraratne S, Konrad I et al. 2012. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J. Exp. Med. 209:4819–35
     [Google Scholar]
  4. 4.
    Koike Y, Tanaka K, Okugawa Y, Morimoto Y, Toiyama Y et al. 2011. In vivo real-time two-photon microscopic imaging of platelet aggregation induced by selective laser irradiation to the endothelium created in the beta-actin-green fluorescent protein transgenic mice. J. Thromb. Thrombolysis 32:2138–45
     [Google Scholar]
  5. 5.
    Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J et al. 2015. Immunosurveillance of the liver by intravascular effector CD8+ T cells. Cell 161:3486–500
     [Google Scholar]
  6. 6.
    Crainiciuc G, Palomino-Segura M, Molina-Moreno M, Sicilia J, Aragones DG et al. 2022. Behavioural immune landscapes of inflammation. Nature 601:7893415–21
     [Google Scholar]
  7. 7.
    Peters NC, Egen JG, Secundino N, Debrabant A, Kimblin N et al. 2008. In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321:5891970–74
     [Google Scholar]
  8. 8.
    Robertson TF, Huttenlocher A. 2022. Real-time imaging of inflammation and its resolution: It's apparent because it's transparent. Immunol. Rev. 306:1258–70
     [Google Scholar]
  9. 9.
    Miskolci V, Tweed KE, Lasarev MR, Britt EC, Walsh AJ et al. 2022. In vivo fluorescence lifetime imaging of macrophage intracellular metabolism during wound responses in zebrafish. eLife 11:e66080
     [Google Scholar]
  10. 10.
    Köhler A, De Filippo K, Hasenberg M, van den Brandt C, Nye E et al. 2011. G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood 117:164349–57
     [Google Scholar]
  11. 11.
    Chiang EY, Hidalgo A, Chang J, Frenette PS. 2007. Imaging receptor microdomains on leukocyte subsets in live mice. Nat. Methods 4:3219–22
     [Google Scholar]
  12. 12.
    Subramanian BC, Melis N, Chen D, Wang W, Gallardo D et al. 2020. The LTB4-BLT1 axis regulates actomyosin and β2-integrin dynamics during neutrophil extravasation. J. Cell Biol. 219:10e201910215
     [Google Scholar]
  13. 13.
    Lämmermann T, Afonso PV, Angermann BR, Wang JM, Kastenmüller W et al. 2013. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature 498:7454371–75
     [Google Scholar]
  14. 14.
    Li JL, Goh CC, Keeble JL, Qin JS, Roediger B et al. 2012. Intravital multiphoton imaging of immune responses in the mouse ear skin. Nat. Protoc. 7:2221–34
     [Google Scholar]
  15. 15.
    Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M et al. 2013. Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and “instruct” them with pattern-recognition and motility programs. Nat. Immunol. 14:141–51
     [Google Scholar]
  16. 16.
    Ng LG, Qin JS, Roediger B, Wang Y, Jain R et al. 2011. Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events. J. Investig. Dermatol. 131:102058–68
     [Google Scholar]
  17. 17.
    Uderhardt S, Martins AJ, Tsang JS, Lämmermann T, Germain RN. 2019. Resident macrophages cloak tissue microlesions to prevent neutrophil-driven inflammatory damage. Cell 177:3541–55.e17
     [Google Scholar]
  18. 18.
    Afonso PV, Janka-Junttila M, Lee YJ, McCann CP, Oliver CM et al. 2012. LTB4 is a signal-relay molecule during neutrophil chemotaxis. Dev. Cell 22:51079–91
     [Google Scholar]
  19. 19.
    Kienle K, Glaser KM, Eickhoff S, Mihlan M, Knöpper K et al. 2021. Neutrophils self-limit swarming to contain bacterial growth in vivo. Science 372:6548eabe7729
     [Google Scholar]
  20. 20.
    Uderhardt S, Knopf J, Herrmann M. 2021. Neutrophil swarm control: What goes up must come down. Signal Transduct. Target. Ther. 6:416
     [Google Scholar]
  21. 21.
    Barkaway A, Rolas L, Joulia R, Bodkin J, Lenn T et al. 2021. Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage. Immunity 54:71494–510.e7
     [Google Scholar]
  22. 22.
    Casanova-Acebes M, Pitaval C, Weiss LA, Nombela-Arrieta C, Chèvre R et al. 2013. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 153:51025–35
     [Google Scholar]
  23. 23.
    Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L et al. 2013. Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153:2362–75
     [Google Scholar]
  24. 24.
    Dal-Secco D, Wang J, Zeng Z, Kolaczkowska E, Wong CHY et al. 2015. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J. Exp. Med. 212:4447–56
     [Google Scholar]
  25. 25.
    Rua R, Lee JY, Silva AB, Swafford IS, Maric D et al. 2019. Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity. Nat. Immunol. 20:4407–19
     [Google Scholar]
  26. 26.
    Kreisel D, Nava RG, Li W, Zinselmeyer BH, Wang B et al. 2010. In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. PNAS 107:4218073–78
     [Google Scholar]
  27. 27.
    Li W, Hsiao H-M, Higashikubo R, Saunders BT, Bharat A et al. 2016. Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling. JCI Insight 1:12e87315
     [Google Scholar]
  28. 28.
    Zindel J, Peiseler M, Hossain M, Deppermann C, Lee WY et al. 2021. Primordial GATA6 macrophages function as extravascular platelets in sterile injury. Science 371:6533eabe0595
     [Google Scholar]
  29. 29.
    Zhang N, Czepielewski RS, Jarjour NN, Erlich EC, Esaulova E et al. 2019. Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity. J. Exp. Med. 216:61291–300
     [Google Scholar]
  30. 30.
    Ginhoux F, Jung S. 2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14:6392–404
     [Google Scholar]
  31. 31.
    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 159:61312–26
     [Google Scholar]
  32. 32.
    Mass E, Ballesteros I, Farlik M, Halbritter F, Günther P et al. 2016. Specification of tissue-resident macrophages during organogenesis. Science 353:6304aaf4238
     [Google Scholar]
  33. 33.
    Liu C, Wu C, Yang Q, Gao J, Li L et al. 2016. Macrophages mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction. Immunity 44:51162–76
     [Google Scholar]
  34. 34.
    Roberts AW, Lee BL, Deguine J, John S, Shlomchik MJ, Barton GM. 2017. Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells. Immunity 47:5913–27.e6
     [Google Scholar]
  35. 35.
    Guilliams M, Bonnardel J, Haest B, Vanderborght B, Wagner C et al. 2022. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell 185:2379–96.e38
     [Google Scholar]
  36. 36.
    McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I et al. 2010. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330:6002362–66
     [Google Scholar]
  37. 37.
    McDonald B, Jenne CN, Zhuo L, Kimata K, Kubes P. 2013. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia. Am. J. Physiol. Gastrointest. Liver Physiol. 305:11G797–806
     [Google Scholar]
  38. 38.
    Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN. 2011. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity 34:5807–19
     [Google Scholar]
  39. 39.
    Wehr A, Baeck C, Heymann F, Niemietz PM, Hammerich L et al. 2013. Chemokine receptor CXCR6-dependent hepatic NK T cell accumulation promotes inflammation and liver fibrosis. J. Immunol. 190:105226–36
     [Google Scholar]
  40. 40.
    Grandjean CL, Montalvao F, Celli S, Michonneau D, Breart B et al. 2016. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies. Sci. Rep. 6:34382
     [Google Scholar]
  41. 41.
    Egen JG, Rothfuchs AG, Feng CG, Winter N, Sher A, Germain RN. 2008. Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 28:2271–84
     [Google Scholar]
  42. 42.
    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 51:4638–54.e9
     [Google Scholar]
  43. 43.
    Kolter J, Feuerstein R, Zeis P, Hagemeyer N, Paterson N et al. 2019. A subset of skin macrophages contributes to the surveillance and regeneration of local nerves. Immunity 50:61482–97.e7
     [Google Scholar]
  44. 44.
    Nimmerjahn A, Kirchhoff F, Helmchen F. 2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:57261314–18
     [Google Scholar]
  45. 45.
    Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P et al. 2005. Dynamics and function of Langerhans cells in vivo: Dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22:5643–54
     [Google Scholar]
  46. 46.
    Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y et al. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8:6752–58
     [Google Scholar]
  47. 47.
    Freeman SA, Uderhardt S, Saric A, Collins RF, Buckley CM et al. 2020. Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance. Science 367:6475301–5
     [Google Scholar]
  48. 48.
    Germain RN, Robey EA, Cahalan MD. 2012. A decade of imaging cellular motility and interaction dynamics in the immune system. Science 336:60891676–81
     [Google Scholar]
  49. 49.
    Allen CDC, Okada T, Tang HL, Cyster JG. 2007. Imaging of germinal center selection events during affinity maturation. Science 315:5811528–31
     [Google Scholar]
  50. 50.
    Hauser AE, Shlomchik MJ, Haberman AM. 2007. In vivo imaging studies shed light on germinal-centre development. Nat. Rev. Immunol. 7:7499–504
     [Google Scholar]
  51. 51.
    Hauser AE, Junt T, Mempel TR, Sneddon MW, Kleinstein SH et al. 2007. Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity 26:5655–67
     [Google Scholar]
  52. 52.
    Kerfoot SM, Yaari G, Patel JR, Johnson KL, Gonzalez DG et al. 2011. Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone. Immunity 34:6947–60
     [Google Scholar]
  53. 53.
    Qi H, Egen JG, Huang AYC, Germain RN. 2006. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312:57801672–76
     [Google Scholar]
  54. 54.
    Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E et al. 2014. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 345:62001058–62
     [Google Scholar]
  55. 55.
    Liu B, Lin Y, Yan J, Yao J, Liu D et al. 2021. Affinity-coupled CCL22 promotes positive selection in germinal centres. Nature 592:7852133–37
     [Google Scholar]
  56. 56.
    Schwickert TA, Lindquist RL, Shakhar G, Livshits G, Skokos D et al. 2007. In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446:713183–87
     [Google Scholar]
  57. 57.
    Mempel TR, Henrickson SE, Von Andrian UH. 2004. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:6970154–59
     [Google Scholar]
  58. 58.
    Arnon TI, Horton RM, Grigorova IL, Cyster JG. 2013. Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress. Nature 493:7434684–88
     [Google Scholar]
  59. 59.
    Baptista AP, Gola A, Huang Y, Milanez-Almeida P, Torabi-Parizi P et al. 2019. The chemoattractant receptor Ebi2 drives intranodal naive CD4+ T cell peripheralization to promote effective adaptive immunity. Immunity 50:51188–201.e6
     [Google Scholar]
  60. 60.
    Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K et al. 2015. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell 162:61322–37
     [Google Scholar]
  61. 61.
    Gerner MY, Casey KA, Kastenmuller W, Germain RN. 2017. Dendritic cell and antigen dispersal landscapes regulate T cell immunity. J. Exp. Med. 214:103105–22
     [Google Scholar]
  62. 62.
    Qi H, Kastenmüller W, Germain RN. 2014. Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue. Annu. Rev. Cell Dev. Biol. 30:141–67
     [Google Scholar]
  63. 63.
    Liu D, Duan L, Rodda LB, Lu E, Xu Y et al. 2022. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. Science 375:6581eabi5965
     [Google Scholar]
  64. 64.
    Heesters BA, Chatterjee P, Kim Y-A, Gonzalez SF, Kuligowski MP et al. 2013. Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity 38:61164–75
     [Google Scholar]
  65. 65.
    Reimer D, Meyer-Hermann M, Rakhymzhan A, Steinmetz T, Tripal P et al. 2020. B cell speed and B-FDC contacts in germinal centers determine plasma cell output via swiprosin-1/EFhd2. Cell Rep 32:6108030
     [Google Scholar]
  66. 66.
    Suzuki K, Grigorova I, Phan TG, Kelly LM, Cyster JG. 2009. Visualizing B cell capture of cognate antigen from follicular dendritic cells. J. Exp. Med. 206:71485–93
     [Google Scholar]
  67. 67.
    Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A et al. 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:2264–76
     [Google Scholar]
  68. 68.
    Moseman EA, Iannacone M, Bosurgi L, Tonti E, Chevrier N et al. 2012. B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity. Immunity 36:3415–26
     [Google Scholar]
  69. 69.
    van der Poel CE, Bajic G, Macaulay CW, van den Broek T, Ellson CD et al. 2019. Follicular dendritic cells modulate germinal center B cell diversity through FcγRIIB. Cell Rep. 29:92745–55.e4
     [Google Scholar]
  70. 70.
    Phan TG, Grigorova I, Okada T, Cyster JG. 2007. Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat. Immunol. 8:9992–1000
     [Google Scholar]
  71. 71.
    Victora GD, Schwickert TA, Fooksman DR, Kamphorst AO, Meyer-Hermann M et al. 2010. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143:4592–605
     [Google Scholar]
  72. 72.
    Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. 2008. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455:7214764–69
     [Google Scholar]
  73. 73.
    Liu D, Yan J, Sun J, Liu B, Ma W et al. 2021. BCL6 controls contact-dependent help delivery during follicular T-B cell interactions. Immunity 54:102245–55.e4
     [Google Scholar]
  74. 74.
    Mayer CT, Gazumyan A, Kara EE, Gitlin AD, Golijanin J et al. 2017. The microanatomic segregation of selection by apoptosis in the germinal center. Science 358:6360eaao2602
     [Google Scholar]
  75. 75.
    Abtin A, Jain R, Mitchell AJ, Roediger B, Brzoska AJ et al. 2014. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nat. Immunol. 15:145–53
     [Google Scholar]
  76. 76.
    Bogoslowski A, Butcher EC, Kubes P. 2018. Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus. PNAS 115:102449–54
     [Google Scholar]
  77. 77.
    Kratofil RM, Shim HB, Shim R, Lee WY, Labit E et al. 2022. A monocyte-leptin-angiogenesis pathway critical for repair post-infection. Nature 609:7925166–73
     [Google Scholar]
  78. 78.
    Coombes JL, Charsar BA, Han S-J, Halkias J, Chan SW et al. 2013. Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread. PNAS 110:21E1913–22
     [Google Scholar]
  79. 79.
    Konradt C, Ueno N, Christian DA, Delong JH, Pritchard GH et al. 2016. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system. Nat. Microbiol. 1:16001
     [Google Scholar]
  80. 80.
    Liu Z, Lu X, Villette V, Gou Y, Colbert KL et al. 2022. Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy. Cell 185:183408–25.e29
     [Google Scholar]
  81. 81.
    Máthé D, Szalay G, Cseri L, Kis Z, Pályi B et al. 2022. Monitoring correlates of SARS-CoV-2 infection in cell culture using two-photon microscopy and a novel fluorescent calcium-sensitive dye. bioRxiv 2022.09.12.506773. https://doi.org/10.1101/2022.09.12.506773
  82. 82.
    Lim K, Kim T-H, Trzeciak A, Amitrano AM, Reilly EC et al. 2020. In situ neutrophil efferocytosis shapes T cell immunity to influenza infection. Nat. Immunol. 21:91046–57
     [Google Scholar]
  83. 83.
    Lambert Emo K, Hyun Y-M, Reilly E, Barilla C, Gerber S et al. 2016. Live imaging of influenza infection of the trachea reveals dynamic regulation of CD8+ T cell motility by antigen. PLOS Pathog. 12:9e1005881
     [Google Scholar]
  84. 84.
    Murooka TT, Deruaz M, Marangoni F, Vrbanac VD, Seung E et al. 2012. HIV-infected T cells are migratory vehicles for viral dissemination. Nature 490:7419283–87
     [Google Scholar]
  85. 85.
    Manning JE, Lewis JW, Marsh L-J, McGettrick HM. 2021. Insights into leukocyte trafficking in inflammatory arthritis—imaging the joint. Front. Cell Dev. Biol. 9:635102
     [Google Scholar]
  86. 86.
    Miyabe Y, Miyabe C, Murooka TT, Kim EY, Newton GA et al. 2017. Complement C5a receptor is the key initiator of neutrophil adhesion igniting immune complex-induced arthritis. Sci. Immunol. 2:7eaaj2195
     [Google Scholar]
  87. 87.
    Hasegawa T, Kikuta J, Sudo T, Yamashita E, Seno S et al. 2020. Development of an intravital imaging system for the synovial tissue reveals the dynamics of CTLA-4 Ig in vivo. Sci. Rep. 10:113480
     [Google Scholar]
  88. 88.
    Furuya M, Kikuta J, Fujimori S, Seno S, Maeda H et al. 2018. Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo. Nat. Commun. 9:1300
     [Google Scholar]
  89. 89.
    Kikuta J, Wada Y, Kowada T, Wang Z, Sun-Wada G-H et al. 2013. Dynamic visualization of RANKL and Th17-mediated osteoclast function. J. Clin. Investig. 123:2866–73
     [Google Scholar]
  90. 90.
    Reed DA, Yotsuya M, Gubareva P, Toth PT, Bertagna A. 2019. Two-photon fluorescence and second harmonic generation characterization of extracellular matrix remodeling in post-injury murine temporomandibular joint osteoarthritis. PLOS ONE 14:3e0214072
     [Google Scholar]
  91. 91.
    Coppieters K, Martinic MM, Kiosses WB, Amirian N, von Herrath M. 2010. A novel technique for the in vivo imaging of autoimmune diabetes development in the pancreas by two-photon microscopy. PLOS ONE 5:12e15732
     [Google Scholar]
  92. 92.
    Lindsay RS, Corbin K, Mahne A, Levitt BE, Gebert MJ et al. 2015. Antigen recognition in the islets changes with progression of autoimmune islet infiltration. J. Immunol. 194:2522–30
     [Google Scholar]
  93. 93.
    Calderon B, Suri A, Miller MJ, Unanue ER. 2008. Dendritic cells in islets of Langerhans constitutively present β cell-derived peptides bound to their class II MHC molecules. PNAS 105:166121–26
     [Google Scholar]
  94. 94.
    Melli K, Friedman RS, Martin AE, Finger EB, Miao G et al. 2009. Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues. J. Immunol. 182:52590–600
     [Google Scholar]
  95. 95.
    Lindsay RS, Whitesell JC, Dew KE, Rodriguez E, Sandor AM et al. 2021. MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites. J. Exp. Med. 218:10e20200464
     [Google Scholar]
  96. 96.
    Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF. 2011. Stabilized imaging of immune surveillance in the mouse lung. Nat. Methods 8:191–96
     [Google Scholar]
  97. 97.
    Fiole D, Deman P, Trescos Y, Mayol J-F, Mathieu J et al. 2014. Two-photon intravital imaging of lungs during anthrax infection reveals long-lasting macrophage-dendritic cell contacts. Infect. Immun. 82:2864–72
     [Google Scholar]
  98. 98.
    Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F et al. 2017. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 11:264–18
     [Google Scholar]
  99. 99.
    Headley MB, Bins A, Nip A, Roberts EW, Looney MR et al. 2016. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 531:7595513–17
     [Google Scholar]
  100. 100.
    Ichise H, Tsukamoto S, Hirashima T, Konishi Y, Oki C et al. 2022. Functional visualization of NK cell-mediated killing of metastatic single tumor cells. eLife 11:e76269
     [Google Scholar]
  101. 101.
    Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M et al. 2018. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat. Med. 24:81178–91
     [Google Scholar]
  102. 102.
    Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C et al. 2012. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 21:3402–17
     [Google Scholar]
  103. 103.
    Di Pilato M, Kfuri-Rubens R, Pruessmann JN, Ozga AJ, Messemaker M et al. 2021. CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment. Cell 184:174512–30.e22
     [Google Scholar]
  104. 104.
    Veres TZ, Kopcsányi T, Tirri M, Braun A, Miyasaka M et al. 2017. Intubation-free in vivo imaging of the tracheal mucosa using two-photon microscopy. Sci. Rep. 7:1694
     [Google Scholar]
  105. 105.
    Canton J, Schlam D, Breuer C, Tschow MGU, Glogauer M, Grinstein S. 2016. Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages. Nat. Commun. 7:11284
     [Google Scholar]
  106. 106.
    Yang J, Li W, Duan M, Zhou Z, Lin N et al. 2005. Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats. Inflamm. Res. 54:3133–37
     [Google Scholar]
  107. 107.
    Lämmermann T, Germain RN. 2014. The multiple faces of leukocyte interstitial migration. Semin. Immunopathol. 36:2227–51
     [Google Scholar]
  108. 108.
    Vintersten K, Monetti C, Gertsenstein M, Zhang P, Laszlo L et al. 2004. Mouse in red: red fluorescent protein expression in mouse ES cells, embryos, and adult animals. Genesis 40:4241–46
     [Google Scholar]
  109. 109.
    Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. 2007. A global double-fluorescent Cre reporter mouse. Genesis 45:9593–605
     [Google Scholar]
  110. 110.
    Ueki H, Wang I-H, Zhao D, Gunzer M, Kawaoka Y. 2020. Multicolor two-photon imaging of in vivo cellular pathophysiology upon influenza virus infection using the two-photon IMPRESS. Nat. Protoc. 15:31041–65
     [Google Scholar]
  111. 111.
    Torabi-Parizi P, Vrisekoop N, Kastenmuller W, Gerner MY, Egen JG, Germain RN. 2014. Pathogen-related differences in the abundance of presented antigen are reflected in CD4+ T cell dynamic behavior and effector function in the lung. J. Immunol. 192:41651–60
     [Google Scholar]
  112. 112.
    Textor J, Peixoto A, Henrickson SE, Sinn M, von Andrian UH, Westermann J. 2011. Defining the quantitative limits of intravital two-photon lymphocyte tracking. PNAS 108:3012401–6
     [Google Scholar]
  113. 113.
    Rahman SMT, Aqdas M, Martin EW, Tomassoni Ardori F, Songkiatisak P et al. 2022. Double knockin mice show NF-κB trajectories in immune signaling and aging. Cell Rep 41:8111682
     [Google Scholar]
  114. 114.
    Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA et al. 2010. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13:1133–40
     [Google Scholar]
  115. 115.
    Clausen BE, Burkhardt C, Reith W, Renkawitz R, Förster I. 1999. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res 8:4265–77
     [Google Scholar]
  116. 116.
    Faust N, Varas F, Kelly LM, Heck S, Graf T. 2000. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96:2719–26
     [Google Scholar]
  117. 117.
    Satpathy AT, KC W, Albring JC, Edelson BT, Kretzer NM et al. 2012. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J. Exp. Med. 209:61135–52
     [Google Scholar]
  118. 118.
    Saederup N, Cardona AE, Croft K, Mizutani M, Cotleur AC et al. 2010. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLOS ONE 5:10e13693
     [Google Scholar]
  119. 119.
    Geissmann F, Cameron TO, Sidobre S, Manlongat N, Kronenberg M et al. 2005. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLOS Biol 3:4e113
     [Google Scholar]
  120. 120.
    Reinhardt RL, Liang H-E, Bao K, Price AE, Mohrs M et al. 2015. A novel model for IFN-γ-mediated autoinflammatory syndromes. J. Immunol. 194:52358–68
     [Google Scholar]
  121. 121.
    Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R et al. 2006. Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25:1129–41
     [Google Scholar]
  122. 122.
    Kamanaka M, Kim ST, Wan YY, Sutterwala FS, Lara-Tejero M et al. 2006. Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse. Immunity 25:6941–52
     [Google Scholar]
  123. 123.
    Bettelli E, Carrier Y, Gao W, Korn T, Strom TB et al. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:7090235–38
     [Google Scholar]
  124. 124.
    Moran AE, Holzapfel KL, Xing Y, Cunningham NR, Maltzman JS et al. 2011. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208:61279–89
     [Google Scholar]
  125. 125.
    Kitano M, Moriyama S, Ando Y, Hikida M, Mori Y et al. 2011. Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity. Immunity 34:6961–72
     [Google Scholar]
  126. 126.
    Fooksman DR, Schwickert TA, Victora GD, Dustin ML, Nussenzweig MC, Skokos D. 2010. Development and migration of plasma cells in the mouse lymph node. Immunity 33:1118–27
     [Google Scholar]
  127. 127.
    Kim J-S, Kolesnikov M, Peled-Hajaj S, Scheyltjens I, Xia Y et al. 2021. A binary Cre transgenic approach dissects microglia and CNS border-associated macrophages. Immunity 54:1176–90.e7
     [Google Scholar]
  128. 128.
    Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN et al. 2008. T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nat. Immunol. 9:3282–91
     [Google Scholar]
  129. 129.
    Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J et al. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Dev. Cell 57:147–62.e9
     [Google Scholar]
  130. 130.
    Hons M, Kopf A, Hauschild R, Leithner A, Gaertner F et al. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nat. Immunol. 19:6606–16
     [Google Scholar]
  131. 131.
    Lim JF, Berger H, Su I-H. 2016. Isolation and activation of murine lymphocytes. J. Vis. Exp. 116:54596
     [Google Scholar]
  132. 132.
    van Panhuys N, Klauschen F, Germain RN. 2014. T-cell-receptor-dependent signal intensity dominantly controls CD4+ T cell polarization in vivo. Immunity 41:163–74
     [Google Scholar]
  133. 133.
    Subramanian S, Busch CJ-L, Molawi K, Geirsdottir L, Maurizio J et al. 2022. Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo. Nat. Immunol. 23:3458–68
     [Google Scholar]
  134. 134.
    Wang J, Kubes P. 2016. A reservoir of mature cavity macrophages that can rapidly invade visceral organs to affect tissue repair. Cell 165:3668–78
     [Google Scholar]
  135. 135.
    Guilliams M, Thierry GR, Bonnardel J, Bajenoff M. 2020. Establishment and maintenance of the macrophage niche. Immunity 52:3434–51
     [Google Scholar]
  136. 136.
    Blériot C, Chakarov S, Ginhoux F. 2020. Determinants of resident tissue macrophage identity and function. Immunity 52:6957–70
     [Google Scholar]
  137. 137.
    Sagoo P, Garcia Z, Breart B, Lemaitre F, Michonneau D et al. 2015. In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity. Nat. Med. 22:164–71
     [Google Scholar]
  138. 138.
    Gerner MY, Torabi-Parizi P, Germain RN. 2015. Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens. Immunity 42:1172–85
     [Google Scholar]
  139. 139.
    Tomura M, Yoshida N, Tanaka J, Karasawa S, Miwa Y et al. 2008. Monitoring cellular movement in vivo with photoconvertible fluorescence protein “Kaede” transgenic mice. PNAS 105:3110871–76
     [Google Scholar]
  140. 140.
    Medaglia C, Giladi A, Stoler-Barak L, De Giovanni M, Salame TM et al. 2017. Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq. Science 358:63701622–26
     [Google Scholar]
  141. 141.
    Ronzitti E, Ventalon C, Canepari M, Forget BC, Papagiakoumou E, Emiliani V. 2017. Recent advances in patterned photostimulation for optogenetics. J. Opt. 19:11113001
     [Google Scholar]
  142. 142.
    Adesnik H, Abdeladim L. 2021. Probing neural codes with two-photon holographic optogenetics. Nat. Neurosci. 24:101356–66
     [Google Scholar]
  143. 143.
    Yang W, Carrillo-Reid L, Bando Y, Peterka DS, Yuste R. 2018. Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions. eLife 7:e32671
     [Google Scholar]
  144. 144.
    Tan P, He L, Han G, Zhou Y. 2017. Optogenetic immunomodulation: shedding light on antitumor immunity. Trends Biotechnol 35:3215–26
     [Google Scholar]
  145. 145.
    Nakai J, Ohkura M, Imoto K. 2001. A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nat. Biotechnol. 19:2137–41
     [Google Scholar]
  146. 146.
    Bohineust A, Garcia Z, Corre B, Lemaître F, Bousso P. 2020. Optogenetic manipulation of calcium signals in single T cells in vivo. Nat. Commun. 11:11143
     [Google Scholar]
  147. 147.
    Kyratsous NI, Bauer IJ, Zhang G, Pesic M, Bartholomäus I et al. 2017. Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy. PNAS 114:31E6381–89
     [Google Scholar]
  148. 148.
    Schaefer PM, Kalinina S, Rueck A, von Arnim CAF, von Einem B. 2019. NADH autofluorescence—a marker on its way to boost bioenergetic research. Cytometry A 95:134–46
     [Google Scholar]
  149. 149.
    Allen CH, Ahmed D, Raiche-Tanner O, Chauhan V, Mostaço-Guidolin L et al. 2021. Label-free two-photon imaging of mitochondrial activity in murine macrophages stimulated with bacterial and viral ligands. Sci. Rep. 11:114081
     [Google Scholar]
  150. 150.
    Ershov D, Phan M-S, Pylvänäinen JW, Rigaud SU, Le Blanc L et al. 2021. Bringing TrackMate into the era of machine-learning and deep-learning. bioRxiv 2021.09.03.458852. https://doi.org/10.1101/2021.09.03.458852
  151. 151.
    Zhao Z, Zhou Y, Liu B, He J, Zhao J et al. 2023. Two-photon synthetic aperture microscopy for minimally invasive fast 3D imaging of native subcellular behaviors in deep tissue. Cell 186:112475–91.e22
     [Google Scholar]
  152. 152.
    Bakker G-J, Weischer S, Ferrer Ortas J, Heidelin J, Andresen V et al. 2022. Intravital deep-tumor single-beam 3-photon, 4-photon, and harmonic microscopy. eLife 11:e63776
     [Google Scholar]
  153. 153.
    Germain RN, Radtke AJ, Thakur N, Schrom EC, Hor JL et al. 2022. Understanding immunity in a tissue-centric context: combining novel imaging methods and mathematics to extract new insights into function and dysfunction. Immunol. Rev. 306:18–24
     [Google Scholar]
  154. 154.
    Bajénoff M, Glaichenhaus N, Germain RN. 2008. Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone. J. Immunol. 181:3947–54
     [Google Scholar]
/content/journals/10.1146/annurev-pathmechdis-070323-124158
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Dynamic Multiplex Tissue Imaging in Inflammation Research
Annual Review of Pathology: Mechanisms of Disease 19, 43 (2024); https://doi.org/10.1146/annurev-pathmechdis-070323-124158
/content/journals/10.1146/annurev-pathmechdis-070323-124158
/content/journals/10.1146/annurev-pathmechdis-070323-124158
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