Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections

Abstract

Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)–skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Il4−/− but not Ifng−/− mice initiate bacterial clearance within three days after bladder infection.
Fig. 2: CD4+ T cells are preferentially differentiated into TH2 cells in the bladder, particularly after a second infection.
Fig. 3: TH2 cells are necessary for superficial bladder epithelium regeneration.
Fig. 4: IL-4-regulated growth factors are important for epithelial repair.
Fig. 5: Tissue resident CD301b+ dendritic cells activate TH2 cells during bladder infection.
Fig. 6: OX40L on CD301b+ DCs is responsible for the induction of TH2 bias in bladder.
Fig. 7: Repeated bladder infections promote TH2-mediated bladder epithelium repair at the expense of bacterial clearance.

Data availability

All data supporting the findings of this study are available within the article and its supplementary information and from the corresponding author upon reasonable request.

References

  1. 1.

    Foxman, B., Barlow, R., D’Arcy, H., Gillespie, B. & Sobel, J. D. Urinary tract infection: self-reported incidence and associated costs. Ann. Epidemiol. 10, 509–515 (2000).

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Silverman, J. A., Schreiber, H. L. IV., Hooton, T. M. & Hultgren, S. J. From physiology to pharmacy: developments in the pathogenesis and treatment of recurrent urinary tract infections. Curr. Urol. Rep. 14, 448–456 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Foxman, B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect. Dis. Clin. North Am. 28, 1–3 (2014).

    PubMed  Article  Google Scholar 

  4. 4.

    Al-Badr, A. & Al-Shaikh, G. Recurrent urinary tract infections management in women: a review. Sultan Qaboos Univ. Med. J. 13, 359–367 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Flores-Mireles, A. L., Walker, J. N., Caparon, M. & Hultgren, S. J. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat. Rev. Microbiol. 13, 269–284 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Chan, C. Y., John, A. L. & Abraham, S. N. Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38, 349–359 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Hooton, T. M. Recurrent urinary tract infection in women. Int. J. Antimicrob. Agents 17, 259–268. (2001).

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Foxman, B. Recurring urinary tract infection: incidence and risk factors. Am. J. Public Health 80, 331–333 (1990).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Ikähelmo, R. et al. Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women. Clin. Infect. Dis. 22, 91–99 (1996).

    Article  Google Scholar 

  10. 10.

    Kaye, M. G., Fox, M. J., Bartlett, J. G., Braman, S. S. & Glassroth, J. The clinical spectrum of Staphylococcus aureus pulmonary infection. Chest 97, 788–792 (1990).

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Mogulkoc, N. et al. Acute purulent exacerbation of chronic obstructive pulmonary disease and Chlamydia pneumoniae infection. Am. J. Respir. Crit. Care Med. 160, 349–353 (1999).

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Caminero, J. A. et al. Exogenous reinfection with tuberculosis on a European island with a moderate incidence of disease. Am. J. Respir. Crit. Care Med. 163, 717–720 (2001).

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Zar, F. A., Bakkanagari, S. R., Moorthi, K. M. & Davis, M. B. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin. Infect. Dis. 45, 302–307 (2007).

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Borody, T. J. et al. Recurrence of duodenal ulcer and Campylobacter pylori infection after eradication. Med. J. Aust. 151, 431–435 (1989).

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Niv, Y. & Hazazi, R. Helicobacter pylori recurrence in developed and developing countries: meta-analysis of 13C-urea breath test follow-up after eradication. Helicobacter 13, 56–61 (2008).

    PubMed  Article  Google Scholar 

  16. 16.

    Abraham, S. N. & Miao, Y. The nature of immune responses to urinary tract infections. Nat. Rev. Immunol. 15, 655–663 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Wu, J., Miao, Y. & Abraham, S. N. The multiple antibacterial activities of the bladder epithelium. Ann. Tranl Med. 5, 35 (2017).

    Article  CAS  Google Scholar 

  18. 18.

    Haraoka, M. et al. Neutrophil recruitment and resistance to urinary tract infection. J. Infect. Dis. 180, 1220–1229 (1999).

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Schiwon, M. et al. Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156, 456–468 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Tittel, A. P. et al. Kidney dendritic cells induce innate immunity against bacterial pyelonephritis. J. Am. Soc. Nephrol. 22, 1435–1441 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Mulvey, M. A., Schilling, J. D. & Hultgren, S. J. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect. Immun. 69, 4572–4579 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Choi, H. W. et al. Loss of bladder epithelium induced by cytolytic mast cell granules. Immunity 45, 1258–1269 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Percival, A., Brumfitt, W. & De Louvois, J. Serum-antibody levels as an indication of clinically inapparent pyelonephritis. Lancet 284, 1027–1033 (1964).

    Article  Google Scholar 

  24. 24.

    Sanford, B. A., Thomas, V. L., Forland, M. A., Carson, S. A. & Shelokov, A. L. Immune response in urinary tract infection determined by radioimmunoassay and immunofluorescence: serum antibody levels against infecting bacterium and Enterobacteriaceae common antigen. J. Clin. Microbiol. 8, 575–579 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Clark, H., Ronald, A. R. & Turck, M. Serum antibody response in renal versus bladder bacteriuria. J. Infect. Dis. 123, 539–543 (1971).

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Ramakrishnan, K. & Scheid, D. C. Diagnosis and management of acute pyelonephritis in adults. Am. Fam. Physician 71, 933–942 (2005).

    PubMed  Google Scholar 

  27. 27.

    Jones-Carson, J., Balish, E. & Uehling, D. T. Susceptibility of immunodeficient gene-knockout mice to urinary tract infection. J. Urol. 161, 338–341 (1999).

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Thumbikat, P., Waltenbaugh, C., Schaeffer, A. J. & Klumpp, D. J. Antigen-specific responses accelerate bacterial clearance in the bladder. J. Immunol. 176, 3080–3086 (2006).

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Mora-Bau, G. et al. Macrophages subvert adaptive immunity to urinary tract infection. PLoS Pathog. 11, e1005044 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Sivick, K. E., Schaller, M. A., Smith, S. N. & Mobley, H. L. The innate immune response to uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection. J. Immunol. 184, 2065–2075 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Curtsinger, J. M. & Mescher, M. F. Inflammatory cytokines as a third signal for T cell activation. Curr. Opin. Immunol. 22, 333–340 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Flynn, S., Toellner, K. M., Raykundalia, C., Goodall, M. & Lane, P. CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1. J. Exp. Med. 188, 297–304 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Macatonia, S. E. et al. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J. Immunol. 154, 5071–5079 (1995).

    CAS  PubMed  Google Scholar 

  34. 34.

    Croft, M., Bradley, L. M. & Swain, S. L. Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J. Immunol. 152, 2675–2685 (1994).

    CAS  PubMed  Google Scholar 

  35. 35.

    Croft, M. & Swain, S. L. Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J. Immunol. 154, 4269–4282 (1995).

    CAS  PubMed  Google Scholar 

  36. 36.

    Julia, V. et al. Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major. J. Immunol. 165, 5637–5645 (2000).

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Hegazy, A. N. et al. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 153, 1320–1337 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Farber, D. L., Yudanin, N. A. & Restifo, N. P. Human memory T cells: generation, compartmentalization and homeostasis. Nat. Rev. Immunol. 14, 24–35 (2014).

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Honda, K. & Littman, D. R. The microbiota in adaptive immune homeostasis and disease. Nature 535, 75–84 (2016).

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Williams, W. B., Han, Q. & Haynes, B. F. Cross-reactivity of HIV vaccine responses and the microbiome. Curr. Opin. HIV AIDS 13, 9–14 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Su, L. F., Kidd, B. A., Han, A., Kotzin, J. J. & Davis, M. M. Virus-specific CD4+ memory-phenotype T cells are abundant in unexposed adults. Immunity 38, 373–383 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Sawicka, E. et al. Inhibition of Th1-and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720. J. Immunol. 171, 6206–6214 (2003).

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Reinhardt, R. L., Liang, H. E. & Locksley, R. M. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat. Immunol. 10, 385–393 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Reinhardt, R. L. et al. A novel model for IFN-γ–mediated autoinflammatory syndromes. J. Immunol. 194, 2358–2368. (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Mohrs, M., Shinkai, K., Mohrs, K. & Locksley, R. M. Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15, 303–311 (2001).

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Hopkins, W. J., Gendron-Fitzpatrick, A., Balish, E. & Uehling, D. T. Time course and host responses to Escherichia coli urinary tract infection in genetically distinct mouse strains. Infect. Immun. 66, 2798–2802. (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Wynn, T. A. Type 2 cytokines: mechanisms and therapeutic strategies. Nat. Rev. Immunol. 15, 271–282 (2015).

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Walker, J. A. & McKenzie, A. N. TH2 cell development and function. Nat. Rev. Immunol. 18, 121–133 (2018).

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Chen, F. et al. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat. Med. 18, 260–266 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Raes, G. et al. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages. J. Leukoc. Biol. 71, 597–602 (2002).

    CAS  PubMed  Google Scholar 

  52. 52.

    Gordon, S. & Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity 32, 593–604 (2010).

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Conway, J. G. et al. Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc. Natl Acad. Sci. USA 102, 16078–16083 (2005).

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    He, H. et al. Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages. Blood 120, 3152–3162 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Klinkert, K. et al. Selective M2 macrophage depletion leads to prolonged inflammation in surgical wounds. Eur. Surgical Res. 58, 109–120 (2017).

    CAS  Article  Google Scholar 

  56. 56.

    Kumamoto, Y. et al. CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39, 733–743 (2013).

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Kumamoto, Y., Denda-Nagai, K., Aida, S., Higashi, N. & Irimura, T. MGL2+ dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo. PloS One 4, e5619 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  58. 58.

    Gao, Y. et al. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39, 722–732 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Connor, L. M., Tang, S. C., Camberis, M., Le Gros, G. & Ronchese, F. Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J. Immunol. 193, 2709–2717 (2014).

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Sokol, C. L., Camire, R. B., Jones, M. C. & Luster, A. D. The chemokine receptor CCR8 promotes the migration of dendritic cells into the lymph node parenchyma to initiate the allergic immune response. Immunity 49, 449–463 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    Amsen, D. et al. Instruction of distinct CD4 T helper cell fates by different Notch ligands on antigen-presenting cells. Cell 117, 515–526 (2004).

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Zhu, J., Yamane, H. & Paul, W. E. Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 28, 445–489 (2009).

    Article  CAS  Google Scholar 

  63. 63.

    Zhu, J. & Paul, W. E. CD4 T cells: fates, functions, and faults. Blood 112, 1557–1569 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Fields, P. E., Kim, S. T. & Flavell, R. A. Cutting edge: changes in histone acetylation at the IL-4 and IFN-γ loci accompany Th1/Th2 differentiation. J. Immunol. 169, 647–650 (2002).

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Bashyam, H. Th1/Th2 cross-regulation and the discovery of IL-10. J. Exp. Med. 204, 237 (2007).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  66. 66.

    Brubaker, L. & Wolfe, A. The urinary microbiota: a paradigm shift for bladder disorders? Curr. Opin. Obstet. Gynecol. 28, 407–412 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Antunes-Lopes, T. et al. The role of urinary microbiota in lower urinary tract dysfunction: a systematic review. Eur. Urol. Focus 6, 361–369 (2020).

    PubMed  Article  Google Scholar 

  68. 68.

    Yeung, C. K., Sreedhar, B., Leung, Y. F. & Sit, K. Y. Correlation between ultrasonographic bladder measurements and urodynamic findings in children with recurrent urinary tract infection. BJU Int. 99, 651–655 (2007).

    PubMed  Article  Google Scholar 

  69. 69.

    Shaikh, N. Recurrent urinary tract infections in children with bladder and bowel dysfunction. Pediatrics 137, e20152982 (2016).

    PubMed Central  Article  Google Scholar 

  70. 70.

    Cho, M. et al. Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of programmed cell death 1 ligand 2–positive dendritic cells in allergic asthma. J. Allergy Clin. Immunol. 142, 530–541 (2018).

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Arifuzzaman, M. et al. MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Sci. Adv. 5, eaav0216 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  72. 72.

    O’Brien, V. P. et al. A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease. Nat. Microbiol. 2, 16196 (2017).

    Article  CAS  Google Scholar 

  73. 73.

    O’Brien, V. P., Dorsey, D. A., Hannan, T. J. & Hultgren, S. J. Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner. PLoS Pathog. 14, e1007457 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  74. 74.

    Normark, S. et al. Genetics of digalactoside-binding adhesin from a uropathogenic Escherichia coli strain. Infect. Immun. 41, 942–949 (1983).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Di Pilato, M. et al. Targeting the CBM complex causes Treg cells to prime tumours for immune checkpoint therapy. Nature 570, 112–116 (2019).

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Geesala, R. et al. Loss of RHBDF2 results in an early-onset spontaneous murine colitis. J. Leukoc. Biol. 105, 767–781 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Levin, R. M. et al. Trypan blue as an indicator of urothelial integrity. Neurourol. Urodyn. 9, 269–279 (1990).

    Article  Google Scholar 

  78. 78.

    Warburton, D. et al. Epigenetic role of epidermal growth factor expression and signalling in embryonic mouse lung morphogenesis. Dev. Biol. 149, 123–133 (1992).

    CAS  PubMed  Article  Google Scholar 

  79. 79.

    Troyer, K. L. et al. Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-α. Gastroenterology 121, 68–78 (2001).

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Marjou, A. E., Delouvée, A., Thiery, J. P. & Radvanyi, F. Involvement of epidermal growth factor receptor in chemically induced mouse bladder tumour progression. Carcinogenesis 2, 2211–2218 (2000).

    Article  Google Scholar 

  81. 81.

    Powell-Braxton, L. et al. IGF-I is required for normal embryonic growth in mice. Genes Dev. 7, 2609–2617 (1993).

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Leighton, P. A., Ingram, R. S., Eggenschwiler, J., Efstratiadis, A. & Tilghman, S. M. Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375, 34–39 (1995).

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. 84.

    Inouye, B. M. et al. Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria. Res. Rep. Urol. 10, 219–225 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Hughes, F. M. et al. NLRP3 promotes diabetic bladder dysfunction and changes in symptom-specific bladder innervation. Diabetes 68, 430–440 (2019).

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

We thank R. Locksley for providing the reporter strains. We thank the Duke Light Microscopy Core Facility, especially Y. Gao, for their expertise and advice in light microscopy imaging. We thank the Flow Cytometry Shared Resource of the Duke Cancer Institute for their assistance with flow cytometry analysis. We also appreciate the help of M.-N. Huang in the design of the flow cytometry panel. The authors acknowledge the support of the US National Institutes of Health grants R01DK121032 and R01DK121969 to S.N.A.

Author information

Affiliations

Authors

Contributions

Studies were designed by J.W. and S.N.A. with help from R.L.R., J.T.P., F.M.H. and Y.M. Experiments were performed by J.W., B.W.H., C.P., G.S.M. and H.W.C. Data were analyzed by J.W. and S.N.A. The manuscript was written by J.W. and S.N.A. All authors contributed to discussions and manuscript review.

Corresponding author

Correspondence to Soman N. Abraham.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Ioana Visan was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figures 1–7.

Reporting Summary

Source data

Source Data Fig. 1

Statistical Source Data.

Source Data Fig. 2

Statistical Source Data.

Source Data Fig. 3

Statistical Source Data.

Source Data Fig. 4

Statistical Source Data.

Source Data Fig. 5

Statistical Source Data.

Source Data Fig. 6

Statistical Source Data.

Source Data Fig. 7

Statistical Source Data.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, J., Hayes, B.W., Phoenix, C. et al. A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections. Nat Immunol 21, 671–683 (2020). https://doi.org/10.1038/s41590-020-0688-3

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing