1932

Abstract

The bladder is a major component of the urinary tract, an organ system that expels metabolic waste and excess water, which necessitates proximity to the external environment and its pathogens. It also houses a commensal microbiome. Therefore, its tissue immunity must resist pathogen invasion while maintaining tolerance to commensals. Bacterial infection of the bladder is common, with half of women globally experiencing one or more episodes of cystitis in their lifetime. Despite this, our knowledge of bladder immunity, particularly in humans, is incomplete. Here we consider the current view of tissue immunity in the bladder, with a focus on defense against infection. The urothelium has robust immune functionality, and its defensive capabilities are supported by resident immune cells, including macrophages, dendritic cells, natural killer cells, and γδ T cells. We discuss each in turn and consider why adaptive immune responses are often ineffective in preventing recurrent infection, as well as areas of priority for future research.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-101220-032117
2022-04-26
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/immunol/40/1/annurev-immunol-101220-032117.html?itemId=/content/journals/10.1146/annurev-immunol-101220-032117&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Standring S 2008. Gray's Anatomy: The Anatomical Basis of Clinical Practice Edinburgh, UK: Churchill Livingstone
  2. 2. 
    Thomas-White K, Forster SC, Kumar N, Van Kuiken M, Putonti C et al. 2018. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nat. Commun. 9:1557
    [Google Scholar]
  3. 3. 
    Wolfe AJ, Toh E, Shibata N, Rong R, Kenton K et al. 2012. Evidence of uncultivated bacteria in the adult female bladder. J. Clin. Microbiol. 50:1376–83
    [Google Scholar]
  4. 4. 
    Whiteside SA, Razvi H, Dave S, Reid G, Burton JP 2015. The microbiome of the urinary tract—a role beyond infection. Nat. Rev. Urol. 12:81–90
    [Google Scholar]
  5. 5. 
    Turner JE, Becker M, Mittrücker HW, Panzer U. 2018. Tissue-resident lymphocytes in the kidney. J. Am. Soc. Nephrol. 29:389–99
    [Google Scholar]
  6. 6. 
    Stewart BJ, Ferdinand JR, Young MD, Mitchell TJ, Loudon KW et al. 2019. Spatiotemporal immune zonation of the human kidney. Science 365:1461–66
    [Google Scholar]
  7. 7. 
    Park J, Shrestha R, Qiu C, Kondo A, Huang S et al. 2018. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 360:758–63
    [Google Scholar]
  8. 8. 
    Lewis SA. 2000. Everything you wanted to know about the bladder epithelium but were afraid to ask. Am. J. Physiol. Renal Physiol. 278:F867–74
    [Google Scholar]
  9. 9. 
    Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT 2009. Uroplakins in urothelial biology, function, and disease. Kidney Int 75:1153–65
    [Google Scholar]
  10. 10. 
    Foxman B, Brown P. 2003. Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. Infect. Dis. Clin. N. Am. 17:227–41
    [Google Scholar]
  11. 11. 
    Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ 2015. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat. Rev. Microbiol. 13:269–84
    [Google Scholar]
  12. 12. 
    Smellie JM, Barratt TM, Chantler C, Gordon I, Prescod NP et al. 2001. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial. Lancet 357:1329–33
    [Google Scholar]
  13. 13. 
    Brandström P, Jodal U, Sillén U, Hansson S. 2011. The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux. J. Pediatr. Urol. 7:594–600
    [Google Scholar]
  14. 14. 
    Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R et al. 2014. Antimicrobial prophylaxis for children with vesicoureteral reflux. N. Engl. J. Med. 370:2367–76
    [Google Scholar]
  15. 15. 
    Keren R, Shaikh N, Pohl H, Gravens-Mueller L, Ivanova A et al. 2015. Risk factors for recurrent urinary tract infection and renal scarring. Pediatrics 136:e13–21
    [Google Scholar]
  16. 16. 
    MacNeill SJ, Ford D, Evans K, Medcalf JF. 2018. Chapter 2 UK renal replacement therapy adult prevalence in 2016: national and centre-specific analyses. Nephron 139:Suppl. 147–74
    [Google Scholar]
  17. 17. 
    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I et al. 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71:209–49
    [Google Scholar]
  18. 18. 
    Castelao JE, Yuan JM, Skipper PL, Tannenbaum SR, Gago-Dominguez M et al. 2001. Gender- and smoking-related bladder cancer risk. J. Natl. Cancer Inst. 93:538–45
    [Google Scholar]
  19. 19. 
    Vaidya A, Soloway MS, Hawke C, Tiguert R, Civantos F 2001. De novo muscle invasive bladder cancer: Is there a change in trend?. J. Urol. 165:47–50
    [Google Scholar]
  20. 20. 
    Hsu I, Vitkus S, Da J, Yeh S. 2013. Role of oestrogen receptors in bladder cancer development. Nat. Rev. Urol. 10:317–26
    [Google Scholar]
  21. 21. 
    Lombard AP, Mudryj M. 2015. The emerging role of the androgen receptor in bladder cancer. Endocr. Relat. Cancer 22:R265–77
    [Google Scholar]
  22. 22. 
    Sanli O, Dobruch J, Knowles MA, Burger M, Alemozaffar M et al. 2017. Bladder cancer. Nat. Rev. Dis. Primers 3:17022
    [Google Scholar]
  23. 23. 
    Morales A, Eidinger D, Bruce AW. 1976. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J. Urol. 116:180–83
    [Google Scholar]
  24. 24. 
    Sylvester RJ, van der Meijden A, Witjes JA, Jakse G, Nonomura N et al. 2005. High-grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urology 66:90–107
    [Google Scholar]
  25. 25. 
    Krausgruber T, Fortelny N, Fife-Gernedl V, Senekowitsch M, Schuster LC et al. 2020. Structural cells are key regulators of organ-specific immune responses. Nature 583:7815296–302
    [Google Scholar]
  26. 26. 
    Hurst RE. 1994. Structure, function, and pathology of proteoglycans and glycosaminoglycans in the urinary tract. World J. Urol. 12:3–10
    [Google Scholar]
  27. 27. 
    Parsons CL, Mulholland SG, Anwar H. 1979. Antibacterial activity of bladder surface mucin duplicated by exogenous glycosaminoglycan (heparin). Infect. Immun. 24:552–57
    [Google Scholar]
  28. 28. 
    Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR 2001. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J. Biol. Chem. 276:9924–30
    [Google Scholar]
  29. 29. 
    Spencer JD, Jackson AR, Li B, Ching CB, Vonau M et al. 2015. Expression and significance of the HIP/PAP and RegIIIγ antimicrobial peptides during mammalian urinary tract infection. PLOS ONE 10:e0144024
    [Google Scholar]
  30. 30. 
    Steigedal M, Marstad A, Haug M, Damas JK, Strong RK et al. 2014. Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection. J. Immunol. 193:6081–89
    [Google Scholar]
  31. 31. 
    Patras KA, Ha AD, Rooholfada E, Olson J, Ramachandra Rao SP et al. 2019. Augmentation of urinary lactoferrin enhances host innate immune clearance of uropathogenic Escherichia coli. J. Innate Immun. 11:481–95
    [Google Scholar]
  32. 32. 
    Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L et al. 2006. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med. 12:636–41
    [Google Scholar]
  33. 33. 
    Jaillon S, Moalli F, Ragnarsdottir B, Bonavita E, Puthia M et al. 2014. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40:621–32
    [Google Scholar]
  34. 34. 
    Le PT, Pearce MM, Zhang S, Campbell EM, Fok CS et al. 2014. IL22 regulates human urothelial cell sensory and innate functions through modulation of the acetylcholine response, immunoregulatory cytokines and antimicrobial peptides: assessment of an in vitro model. PLOS ONE 9:e111375
    [Google Scholar]
  35. 35. 
    Thumbikat P, Berry RE, Zhou G, Billips BK, Yaggie RE et al. 2009. Bacteria-induced uroplakin signaling mediates bladder response to infection. PLOS Pathog 5:e1000415
    [Google Scholar]
  36. 36. 
    Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC et al. 1998. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282:1494–97
    [Google Scholar]
  37. 37. 
    Song J, Bishop BL, Li G, Grady R, Stapleton A, Abraham SN 2009. TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. PNAS 106:14966–71
    [Google Scholar]
  38. 38. 
    Miao Y, Li G, Zhang X, Xu H, Abraham SN. 2015. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell 161:1306–19
    [Google Scholar]
  39. 39. 
    Steinert EM, Schenkel JM, Fraser KA, Beura LK, Manlove LS et al. 2015. Quantifying memory CD8 T cells reveals regionalization of immunosurveillance. Cell 161:737–49
    [Google Scholar]
  40. 40. 
    Masopust D, Vezys V, Marzo AL, Lefrançois L. 2001. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291:2413–17
    [Google Scholar]
  41. 41. 
    Gebhardt T, Whitney PG, Zaid A, Mackay LK, Brooks AG et al. 2011. Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 477:216–19
    [Google Scholar]
  42. 42. 
    Iijima N, Iwasaki A. 2014. T cell memory: A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells. Science 346:93–98
    [Google Scholar]
  43. 43. 
    Ginhoux F, Guilliams M. 2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44:439–49
    [Google Scholar]
  44. 44. 
    Rous P. 1909. Parabiosis as a test for circulating anti-bodies in cancer: first paper. J. Exp. Med. 11:810–14
    [Google Scholar]
  45. 45. 
    Gasteiger G, Fan X, Dikiy S, Lee SY, Rudensky AY 2015. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science 350:981–85
    [Google Scholar]
  46. 46. 
    Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS. 2012. Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity. Nature 483:227–31
    [Google Scholar]
  47. 47. 
    Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrançois L, Farber DL 2011. Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 187:5510–14
    [Google Scholar]
  48. 48. 
    Anderson KG, Mayer-Barber K, Sung H, Beura L, James BR et al. 2014. Intravascular staining for discrimination of vascular and tissue leukocytes. Nat. Protoc. 9:209–22
    [Google Scholar]
  49. 49. 
    Mackay LK, Braun A, Macleod BL, Collins N, Tebartz C et al. 2015. Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention. J. Immunol. 194:2059–63
    [Google Scholar]
  50. 50. 
    Masopust D, Vezys V, Wherry EJ, Barber DL, Ahmed R. 2006. Cutting edge: Gut microenvironment promotes differentiation of a unique memory CD8 T cell population. J. Immunol. 176:2079–83
    [Google Scholar]
  51. 51. 
    Cheuk S, Schlums H, Gallais Sérézal I, Martini E, Chiang SC et al. 2017. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity 46:287–300
    [Google Scholar]
  52. 52. 
    Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P et al. 2013. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 38:187–97
    [Google Scholar]
  53. 53. 
    Thome JJ, Yudanin N, Ohmura Y, Kubota M, Grinshpun B et al. 2014. Spatial map of human T cell compartmentalization and maintenance over decades of life. Cell 159:814–28
    [Google Scholar]
  54. 54. 
    Clark RA, Watanabe R, Teague JE, Schlapbach C, Tawa MC et al. 2012. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci. Transl. Med. 4:117ra7
    [Google Scholar]
  55. 55. 
    Watanabe R, Gehad A, Yang C, Scott LL, Teague JE et al. 2015. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci. Transl. Med. 7:279ra39
    [Google Scholar]
  56. 56. 
    Wong MT, Ong DE, Lim FS, Teng KW, McGovern N et al. 2016. A high-dimensional atlas of human T cell diversity reveals tissue-specific trafficking and cytokine signatures. Immunity 45:442–56
    [Google Scholar]
  57. 57. 
    Dogra P, Rancan C, Ma W, Toth M, Senda T et al. 2020. Tissue determinants of human NK cell development, function, and residence. Cell 180:749–63.e13
    [Google Scholar]
  58. 58. 
    Gautier EL, Shay T, Miller J, Greter M, Jakubzick C et al. 2012. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13:1118–28
    [Google Scholar]
  59. 59. 
    Mora-Bau G, Platt AM, van Rooijen N, Randolph GJ, Albert ML, Ingersoll MA 2015. Macrophages subvert adaptive immunity to urinary tract infection. PLOS Pathog 11:e1005044
    [Google Scholar]
  60. 60. 
    Zychlinsky Scharff A, Rousseau M, Lacerda Mariano L, Canton T, Consiglio CR et al. 2019. Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection. JCI Insight 5:e122998
    [Google Scholar]
  61. 61. 
    Yu Z, Liao J, Chen Y, Zou C, Zhang H et al. 2019. Single-cell transcriptomic map of the human and mouse bladders. J. Am. Soc. Nephrol. 30:2159–76
    [Google Scholar]
  62. 62. 
    Stewart BJ, Ferdinand JR, Clatworthy MR 2020. Using single-cell technologies to map the human immune system—implications for nephrology. Nat. Rev. Nephrol. 16:112–28
    [Google Scholar]
  63. 63. 
    Young MD, Mitchell TJ, Vieira Braga FA, Tran MGB, Stewart BJ et al. 2018. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. Science 361:594–99
    [Google Scholar]
  64. 64. 
    Victorino F, Sojka DK, Brodsky KS, McNamee EN, Masterson JC et al. 2015. Tissue-resident NK cells mediate ischemic kidney injury and are not depleted by anti-asialo-GM1 antibody. J. Immunol. 195:4973–85
    [Google Scholar]
  65. 65. 
    Lever JM, Hull TD, Boddu R, Pepin ME, Black LM et al. 2019. Resident macrophages reprogram toward a developmental state after acute kidney injury. JCI Insight 4:e125503
    [Google Scholar]
  66. 66. 
    Tabula Muris Consort. (Overall Coord., Logist. Coord., Organ Collect. Process., Libr. Prep. Seq., Comput. Data Anal., Cell Type Annot., Writ. Group, Suppl. Text Writ. Group) Barres BA, Beachy PA, Chan CKF, Clarke MF et al. 2018. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 562:367–72
    [Google Scholar]
  67. 67. 
    Chen Z, Zhou L, Liu L, Hou Y, Xiong M et al. 2020. Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nat. Commun. 11:5077
    [Google Scholar]
  68. 68. 
    Ligon MM, Wang C, DeJong EN, Schulz C, Bowdish DME, Mysorekar IU. 2020. Single cell and tissue-transcriptomic analysis of murine bladders reveals age- and TNFα-dependent but microbiota-independent tertiary lymphoid tissue formation. Mucosal Immunol 13:908–18
    [Google Scholar]
  69. 69. 
    Sato Y, Yanagita M. 2019. Immunology of the ageing kidney. Nat. Rev. Nephrol. 15:625–40
    [Google Scholar]
  70. 70. 
    Tabula Muris Consort 2020. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature 583590–95
  71. 71. 
    van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. 1972. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 46:845–52
    [Google Scholar]
  72. 72. 
    van Furth R. 1976. Macrophage activity and clinical immunology: origin and kinetics of mononuclear phagocytes. Ann. N. Y. Acad. Sci. 278:161–75
    [Google Scholar]
  73. 73. 
    Ginhoux F, Greter M, Leboeuf M, Nandi S, See P et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–45
    [Google Scholar]
  74. 74. 
    Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N et al. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90
    [Google Scholar]
  75. 75. 
    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]
  76. 76. 
    Yona S, Kim KW, Wolf Y, Mildner A, Varol D et al. 2013. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38:79–91
    [Google Scholar]
  77. 77. 
    Jantsch J, Binger KJ, Müller DN, Titze J. 2014. Macrophages in homeostatic immune function. Front. Physiol. 5:146
    [Google Scholar]
  78. 78. 
    Scott EW, Simon MC, Anastasi J, Singh H 1994. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265:1573–77
    [Google Scholar]
  79. 79. 
    Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S et al. 1990. The murine mutation osteope-trosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345:442–44
    [Google Scholar]
  80. 80. 
    Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q et al. 2010. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116:829–40
    [Google Scholar]
  81. 81. 
    Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR et al. 2017. Macrophages facilitate electrical conduction in the heart. Cell 169:510–22.e20
    [Google Scholar]
  82. 82. 
    Muller PA, Koscso B, Rajani GM, Stevanovic K, Berres ML et al. 2014. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158:300–13
    [Google Scholar]
  83. 83. 
    Hume DA, Perry VH, Gordon S 1984. The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia. Anat. Rec. 210:503–12
    [Google Scholar]
  84. 84. 
    Wong YC, Buck RC. 1971. Langerhans cells in epidermoid metaplasia. J. Investig. Dermatol. 56:10–17
    [Google Scholar]
  85. 85. 
    Schiwon M, Weisheit C, Franken L, Gutweiler S, Dixit A et al. 2014. Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156:456–68
    [Google Scholar]
  86. 86. 
    Mariano LL, Rousseau M, Varet H, Legendre R, Gentek R et al. 2020. Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder. Sci. Adv. 6:eabc5739
    [Google Scholar]
  87. 87. 
    Chakarov S, Lim HY, Tan L, Lim SY, See P et al. 2019. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science 363:eaau0964
    [Google Scholar]
  88. 88. 
    Gabanyi I, Muller PA, Feighery L, Oliveira TY, Costa-Pinto FA, Mucida D. 2016. Neuro-immune interactions drive tissue programming in intestinal macrophages. Cell 164:378–91
    [Google Scholar]
  89. 89. 
    Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. 2013. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229:176–85
    [Google Scholar]
  90. 90. 
    Bosurgi L, Cao YG, Cabeza-Cabrerizo M, Tucci A, Hughes LD et al. 2017. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science 356:1072–76
    [Google Scholar]
  91. 91. 
    Lacerda Mariano L, Ingersoll MA 2020. The immune response to infection in the bladder. Nat. Rev. Urol. 17:439–58
    [Google Scholar]
  92. 92. 
    Soehnlein O, Lindbom L. 2010. Phagocyte partnership during the onset and resolution of inflammation. Nat. Rev. Immunol. 10:427–39
    [Google Scholar]
  93. 93. 
    Han H, Roberts J, Lou O, Muller WA, Nathan N, Nathan C 2006. Chemical inhibitors of TNF signal transduction in human neutrophils point to distinct steps in cell activation. J. Leukoc. Biol. 79:147–54
    [Google Scholar]
  94. 94. 
    Merad M, Sathe P, Helft J, Miller J, Mortha A. 2013. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31:563–604
    [Google Scholar]
  95. 95. 
    Weisheit CK, Engel DR, Kurts C. 2015. Dendritic cells and macrophages: sentinels in the kidney. Clin. J. Am. Soc. Nephrol. 10:1841–51
    [Google Scholar]
  96. 96. 
    Tittel AP, Heuser C, Ohliger C, Knolle PA, Engel DR, Kurts C. 2011. Kidney dendritic cells induce innate immunity against bacterial pyelonephritis. J. Am. Soc. Nephrol. 22:1435–41
    [Google Scholar]
  97. 97. 
    MacLean JA, Xia W, Pinto CE, Zhao L, Liu HW, Kradin RL. 1996. Sequestration of inhaled particulate antigens by lung phagocytes: a mechanism for the effective inhibition of pulmonary cell-mediated immunity. Am. J. Pathol. 148:657–66
    [Google Scholar]
  98. 98. 
    Elieh Ali Komi D, Wohrl S, Bielory L 2020. Mast cell biology at molecular level: a comprehensive review. Clin. Rev. Allergy Immunol. 58:342–65
    [Google Scholar]
  99. 99. 
    Pal S, Nath S, Meininger CJ, Gashev AA. 2020. Emerging roles of mast cells in the regulation of lymphatic immuno-physiology. Front. Immunol. 11:1234
    [Google Scholar]
  100. 100. 
    Shelburne CP, Nakano H, St. John AL, Chan C, McLachlan JB et al. 2009. Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues. Cell Host Microbe 6:331–42
    [Google Scholar]
  101. 101. 
    Padawer J. 1974. Mast cells: extended lifespan and lack of granule turnover under normal in vivo conditions. Exp. Mol. Pathol. 20:269–80
    [Google Scholar]
  102. 102. 
    Kitamura Y, Shimada M, Hatanaka K, Miyano Y. 1977. Development of mast cells from grafted bone marrow cells in irradiated mice. Nature 268:442–43
    [Google Scholar]
  103. 103. 
    Kitamura Y, Matsuda H, Hatanaka K. 1979. Clonal nature of mast-cell clusters formed in W/Wv mice after bone marrow transplantation. Nature 281:154–55
    [Google Scholar]
  104. 104. 
    Gentek R, Ghigo C, Hoeffel G, Bulle MJ, Msallam R et al. 2018. Hemogenic endothelial fate mapping reveals dual developmental origin of mast cells. Immunity 48:1160–71.e5
    [Google Scholar]
  105. 105. 
    Li Z, Liu S, Xu J, Zhang X, Han D et al. 2018. Adult connective tissue-resident mast cells originate from late erythro-myeloid progenitors. Immunity 49:640–53.e5
    [Google Scholar]
  106. 106. 
    Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ. 2007. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat. Immunol. 8:1095–104
    [Google Scholar]
  107. 107. 
    Abraham SN, St. John AL. 2010. Mast cell-orchestrated immunity to pathogens. Nat. Rev. Immunol. 10:440–52
    [Google Scholar]
  108. 108. 
    Chan CY, St. John AL, Abraham SN 2013. Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38:349–59
    [Google Scholar]
  109. 109. 
    Choi HW, Bowen SE, Miao Y, Chan CY, Miao EA et al. 2016. Loss of bladder epithelium induced by cytolytic mast cell granules. Immunity 45:1258–69
    [Google Scholar]
  110. 110. 
    Eberl G, Colonna M, Di Santo JP, McKenzie AN. 2015. Innate lymphoid cells: a new paradigm in immunology. Science 348:aaa6566
    [Google Scholar]
  111. 111. 
    Walker JA, McKenzie AN. 2013. Development and function of group 2 innate lymphoid cells. Curr. Opin. Immunol. 25:148–55
    [Google Scholar]
  112. 112. 
    Melo-Gonzalez F, Hepworth MR. 2017. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells. Immunology 150:265–75
    [Google Scholar]
  113. 113. 
    Sivick KE, Schaller MA, Smith SN, Mobley HL. 2010. The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection. J. Immunol. 184:2065–75
    [Google Scholar]
  114. 114. 
    Chevalier MF, Trabanelli S, Racle J, Salome B, Cesson V et al. 2017. ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence. J. Clin. Investig. 127:2916–29
    [Google Scholar]
  115. 115. 
    Abedini A, Zhu YO, Chatterjee S, Halasz G, Devalaraja-Narashimha K et al. 2021. Urinary single-cell profiling captures the cellular diversity of the kidney. J. Am. Soc. Nephrol. 32:614–27
    [Google Scholar]
  116. 116. 
    Rosenberg EB, Herberman RB, Levine PH, Halterman RH, McCoy JL, Wunderlich JR. 1972. Lymphocyte cytotoxicity reactions to leukemia-associated antigens in identical twins. Int. J. Cancer 9:648–58
    [Google Scholar]
  117. 117. 
    Joncker NT, Fernandez NC, Treiner E, Vivier E, Raulet DH. 2009. NK cell responsiveness is tuned commensurate with the number of inhibitory receptors for self-MHC class I: the rheostat model. J. Immunol. 182:4572–80
    [Google Scholar]
  118. 118. 
    Nagler A, Lanier LL, Cwirla S, Phillips JH 1989. Comparative studies of human FcRIII-positive and negative natural killer cells. J. Immunol. 143:3183–91
    [Google Scholar]
  119. 119. 
    Chidrawar SM, Khan N, Chan YL, Nayak L, Moss PA 2006. Ageing is associated with a decline in peripheral blood CD56bright NK cells. Immun. Ageing 3:10
    [Google Scholar]
  120. 120. 
    Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M et al. 2018. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563:347–53
    [Google Scholar]
  121. 121. 
    Peng H, Jiang X, Chen Y, Sojka DK, Wei H et al. 2013. Liver-resident NK cells confer adaptive immunity in skin-contact inflammation. J. Clin. Investig. 123:1444–56
    [Google Scholar]
  122. 122. 
    Carlyle JR, Mesci A, Ljutic B, Belanger S, Tai LH et al. 2006. Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells. J. Immunol. 176:7511–24
    [Google Scholar]
  123. 123. 
    Walzer T, Bléry M, Chaix J, Fuseri N, Chasson L et al. 2007. Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46. PNAS 104:3384–89
    [Google Scholar]
  124. 124. 
    Gur C, Coppenhagen-Glazer S, Rosenberg S, Yamin R, Enk J et al. 2013. Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells. Cell Host Microbe 14:664–74
    [Google Scholar]
  125. 125. 
    Isaacson B, Hadad T, Glasner A, Gur C, Granot Z et al. 2017. Stromal cell-derived factor 1 mediates immune cell attraction upon urinary tract infection. Cell Rep 20:40–47
    [Google Scholar]
  126. 126. 
    Mian MF, Lauzon NM, Andrews DW, Lichty BD, Ashkar AA. 2010. FimH can directly activate human and murine natural killer cells via TLR4. Mol. Ther. 18:1379–88
    [Google Scholar]
  127. 127. 
    Yu L, O'Brien VP, Livny J, Dorsey D, Bandyopadhyay N et al. 2019. Mucosal infection rewires TNFɑ signaling dynamics to skew susceptibility to recurrence. eLife 8:e46677
    [Google Scholar]
  128. 128. 
    Sundac L, Dando SJ, Sullivan MJ, Derrington P, Gerrard J, Ulett GC 2016. Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis. Pathog. Dis. 74:ftw062
    [Google Scholar]
  129. 129. 
    Nagamatsu K, Hannan TJ, Guest RL, Kostakioti M, Hadjifrangiskou M et al. 2015. Dysregulation of Escherichia coli α-hemolysin expression alters the course of acute and persistent urinary tract infection. PNAS 112:E871–80
    [Google Scholar]
  130. 130. 
    Siegfried L, Kmetova M, Puzova H, Molokacova M, Filka J. 1994. Virulence-associated factors in Escherichia coli strains isolated from children with urinary tract infections. J. Med. Microbiol. 41:127–32
    [Google Scholar]
  131. 131. 
    Mukherjee N, Ji N, Hurez V, Curiel TJ, Montgomery MO et al. 2018. Intratumoral CD56. Oncotarget 9:36492–502
    [Google Scholar]
  132. 132. 
    Brandau S, Böhle A. 2001. Activation of natural killer cells by Bacillus Calmette-Guérin. Eur. Urol. 39:518–24
    [Google Scholar]
  133. 133. 
    Brandau S, Riemensberger J, Jacobsen M, Kemp D, Zhao W et al. 2001. NK cells are essential for effective BCG immunotherapy. Int. J. Cancer 92:697–702
    [Google Scholar]
  134. 134. 
    Gao Y, Williams AP. 2015. Role of innate T cells in anti-bacterial immunity. Front. Immunol. 6:302
    [Google Scholar]
  135. 135. 
    Ribot JC, Lopes N, Silva-Santos B. 2021. γδ T cells in tissue physiology and surveillance. Nat. Rev. Immunol. 21:221–32
    [Google Scholar]
  136. 136. 
    Jones-Carson J, Balish E, Uehling DT 1999. Susceptibility of immunodeficient gene-knockout mice to urinary tract infection. J. Urol. 161:338–41
    [Google Scholar]
  137. 137. 
    Suttmann H, Riemensberger J, Bentien G, Schmaltz D, Stöckle M et al. 2006. Neutrophil granulocytes are required for effective Bacillus Calmette-Guérin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res 66:8250–57
    [Google Scholar]
  138. 138. 
    Takeuchi A, Dejima T, Yamada H, Shibata K, Nakamura R et al. 2011. IL-17 production by γδ T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer. Eur. J. Immunol. 41:246–51
    [Google Scholar]
  139. 139. 
    Cui Y, Franciszkiewicz K, Mburu YK, Mondot S, Le Bourhis L et al. 2015. Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation. J. Clin. Investig. 125:4171–85
    [Google Scholar]
  140. 140. 
    Terpstra ML, Remmerswaal EBM, van der Bom-Baylon ND, Sinnige MJ, Kers J et al. 2020. Tissue-resident mucosal-associated invariant T (MAIT) cells in the human kidney represent a functionally distinct subset. Eur. J. Immunol. 50:1783–97
    [Google Scholar]
  141. 141. 
    Hayes BW, Abraham SN. 2016. Innate immune responses to bladder infection. Microbiol. Spectr. 4: https://doi.org/10.1128/microbiolspec.UTI-0024-2016
    [Crossref] [Google Scholar]
  142. 142. 
    O'Brien VP, Dorsey DA, Hannan TJ, Hultgren SJ. 2018. Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner. PLOS Pathog 14:e1007457
    [Google Scholar]
  143. 143. 
    Oh DY, Kwek SS, Raju SS, Li T, McCarthy E et al. 2020. Intratumoral CD4. Cell 181:1612–25.e13
    [Google Scholar]
  144. 144. 
    Ratliff TL, Ritchey JK, Yuan JJ, Andriole GL, Catalona WJ. 1993. T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J. Urol. 150:1018–23
    [Google Scholar]
  145. 145. 
    Geherin SA, Gomez D, Glabman RA, Ruthel G, Hamann A, Debes GF. 2016. IL-10+ innate-like B cells are part of the skin immune system and require α4β1 integrin to migrate between the peritoneum and inflamed skin. J. Immunol. 2514:2514–25
    [Google Scholar]
  146. 146. 
    Stark AK, Chandra A, Chakraborty K, Alam R, Carbonaro V et al. 2018. PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner. Nat. Commun. 9:3174
    [Google Scholar]
  147. 147. 
    James-Ellison MY, Roberts R, Verrier-Jones K, Williams JD, Topley N 1997. Mucosal immunity in the urinary tract: changes in sIgA, FSC and total IgA with age and in urinary tract infection. Clin. Nephrol. 48:69–78
    [Google Scholar]
  148. 148. 
    Mestecky J, McGhee JR. 1987. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv. Immunol. 40:153–245
    [Google Scholar]
  149. 149. 
    Trinchieri A, Braceschi L, Tiranti D, Dell'Acqua S, Mandressi A, Pisani E 1990. Secretory immunoglobulin A and inhibitory activity of bacterial adherence to epithelial cells in urine from patients with urinary tract infections. Urol. Res. 18:305–8
    [Google Scholar]
  150. 150. 
    Svanborg-Edén C, Svennerholm AM. 1978. Secretory immunoglobulin A and G antibodies prevent adhesion of Escherichia coli to human urinary tract epithelial cells. Infect. Immun. 22:790–97
    [Google Scholar]
  151. 151. 
    Floege J, Böddeker M, Stolte H, Koch KM. 1990. Urinary IgA, secretory IgA and secretory component in women with recurrent urinary tract infections. Nephron 56:50–55
    [Google Scholar]
  152. 152. 
    Ethel S, Bhat GK, Hegde BM. 2006. Bacterial adherence and humoral immune response in women with symptomatic and asymptomatic urinary tract infection. Indian J. Med. Microbiol. 24:30–33
    [Google Scholar]
  153. 153. 
    Jodal U, Ahlstedt S, Carlsson B, Hanson LA, Lindberg U, Sohl A. 1974. Local antibodies in childhood urinary tract infection: a preliminary study. Int. Arch. Allergy Appl. Immunol. 47:537–46
    [Google Scholar]
  154. 154. 
    Ratner JJ, Thomas VL, Sanford BA, Forland M. 1981. Bacteria-specific antibody in the urine of patients with acute pyelonephritis and cystitis. J. Infect. Dis. 143:404–12
    [Google Scholar]
  155. 155. 
    Percival A, Birumfitt W, Delouvois J 1964. Serum-antibody levels as an indication of clinically inapparent pyelonephritis. Lancet 2:1027–33
    [Google Scholar]
  156. 156. 
    Thumbikat P, Waltenbaugh C, Schaeffer AJ, Klumpp DJ. 2006. Antigen-specific responses accelerate bacterial clearance in the bladder. J. Immunol. 176:3080–86
    [Google Scholar]
  157. 157. 
    Nielubowicz GR, Mobley HL. 2010. Host-pathogen interactions in urinary tract infection. Nat. Rev. Urol. 7:430–41
    [Google Scholar]
  158. 158. 
    Pastorello I, Rossi Paccani S, Rosini R, Mattera R, Ferrer Navarro M et al. 2013. EsiB, a novel pathogenic Escherichia coli secretory immunoglobulin A-binding protein impairing neutrophil activation. mBio 4:e00206–13
    [Google Scholar]
  159. 159. 
    Hopkins WJ, James LJ, Balish E, Uehling DT 1993. Congenital immunodeficiencies in mice increase susceptibility to urinary tract infection. J. Urol. 149:922–25
    [Google Scholar]
  160. 160. 
    Loubet P, Ranfaing J, Dinh A, Dunyach-Remy C, Bernard L et al. 2020. Alternative therapeutic options to antibiotics for the treatment of urinary tract infections. Front. Microbiol. 11:1509
    [Google Scholar]
  161. 161. 
    Aziminia N, Hadjipavlou M, Philippou Y, Pandian SS, Malde S, Hammadeh MY 2019. Vaccines for the prevention of recurrent urinary tract infections: a systematic review. BJU Int 123:753–68
    [Google Scholar]
  162. 162. 
    Billips BK, Yaggie RE, Cashy JP, Schaeffer AJ, Klumpp DJ. 2009. A live-attenuated vaccine for the treatment of urinary tract infection by uropathogenic Escherichia coli. J. Infect. Dis. 200:263–72
    [Google Scholar]
  163. 163. 
    Wu J, Bao C, Reinhardt RL, Abraham SN. 2021. Local induction of bladder Th1 responses to combat urinary tract infections. PNAS 118:e2026461118
    [Google Scholar]
  164. 164. 
    Wu J, Hayes BW, Phoenix C, Macias GS, Miao Y et al. 2020. A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections. Nat. Immunol. 21:671–83
    [Google Scholar]
  165. 165. 
    Regev A, Teichmann SA, Lander ES, Amit I, Benoist C et al. 2017. The Human Cell Atlas. eLife 6:e27041
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-101220-032117
Loading
/content/journals/10.1146/annurev-immunol-101220-032117
Loading

Data & Media loading...

  • Article Type: Review Article
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