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.

  • Review Article
  • Published:

Immunity to uropathogens: the emerging roles of inflammasomes

Nature Reviews Urology volume 14, pages 284–295 (2017)Cite this article

Subjects

Key Points

  • The NLRP3 inflammasome is activated during infection with uropathogenic Escherichia coli (UPEC) in an α-haemolysin-dependent manner, and exaggerated activation of this inflammasome can cause symptomatic infection

  • Inflammasome-dependent pyroptosis promotes exfoliation of UPEC-infected urothelial cells, thereby resolving the infection and reducing the incidence of chronic cystitis; however, pyroptosis might also increase latency by permitting microbial access to deeper urothelial layers

  • Autophagy dampens IL-1β-release and endorses UPEC latency by promoting the establishment of quiescent intracellular reservoirs (QIRs), which are reduced in cells in which autophagy is defective

  • Group B Streptococcus activates the NLRP3 inflammasome, which is dependent on β-haemolysin-mediated lysosomal leakage and RNA escape; however, the mechanistic details remain unclear

  • IL-1β levels are markedly enhanced during acute pyelonephritis, and could serve as a diagnostic marker for acute pyelonephritis

  • Inflammasome activation and IL-1β secretion have important roles in various murine models of bladder inflammation, representing viable pharmaceutical targets

Abstract

Urinary tract infections (UTIs) cause a huge burden of morbidity worldwide with recurrent UTIs becoming increasingly frequent owing to the emergence of antibiotic-resistant bacterial strains. Interactions between the innate and adaptive immune responses to pathogens colonizing the urinary tract have been the focus of much research. Inflammasomes are part of the innate immune defence and can respond rapidly to infectious insult. Assembly of the multiprotein inflammasome complex activates caspase-1, processes proinflammatory cytokines IL-1β and IL-18, and induces pyroptosis. These effector pathways, in turn, act at different levels to either prevent or resolve infection, or eliminate the infectious agent itself. In certain instances, inflammasome activation promotes tissue pathology; however, the precise functions of inflammasomes in UTIs remain unexplored. An improved understanding of inflammasomes could provide novel approaches for the design of diagnostics and therapeutics for complicated UTIs, enabling us to overcome the challenge of drug resistance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Activation of inflammasomes by uropathogens.
Figure 2: Pyroptosis promotes urothelium exfoliation in UPEC infection.
Figure 3: Autophagy dampens IL-1β-release and promotes recurrent UPEC infection.

Similar content being viewed by others

References

  1. Foxman, B. & Frerichs, R. R. Epidemiology of urinary tract infection: I. Diaphragm use and sexual intercourse. Am. J. Public Health 75, 1308–1313 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hanna-Wakim, R. H. et al. Epidemiology and characteristics of urinary tract infections in children and adolescents. Front. Cell. Infect. Microbiol. 5, 45 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. 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).

    Article  CAS  PubMed  Google Scholar 

  5. Dielubanza, E. J. & Schaeffer, A. J. Urinary tract infections in women. Med. Clin. North Am. 95, 27–41 (2011).

    Article  PubMed  Google Scholar 

  6. Dwyer, P. L. & O'Reilly, M. Recurrent urinary tract infection in the female. Curr. Opin. Obstet. Gynecol. 14, 537–543 (2002).

    Article  PubMed  Google Scholar 

  7. Geerlings, S. E., Beerepoot, M. A. J. & Prins, J. M. Prevention of recurrent urinary tract infections in women. Antimicrobial and nonantimicrobial strategies. Infect. Dis. Clin. North Am. 28, 135–147 (2014).

    Article  PubMed  Google Scholar 

  8. Stamm, W. E. & Norrby, S. R. Urinary tract infections: disease panorama and challenges. J. Infect. Dis. 183 (Suppl. 1), S1–S4 (2001).

    Article  PubMed  Google Scholar 

  9. Fleming, E., Heil, E. L. & Hynicka, L. M. Treatment strategy for a multidrug-resistant Klebsiella UTI. Ann. Pharmacother. 48, 123–127 (2014).

    Article  PubMed  Google Scholar 

  10. Colodner, R., Kometiani, I., Chazan, B. & Raz, R. Risk factors for community-acquired urinary tract infection due to quinolone-resistant E. coli. Infection 36, 41–45 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Paschke, A. A., Zaoutis, T., Conway, P. H., Xie, D., Keren, R. Previous antimicrobial exposure is associated with drug-resistant urinary tract infections in children. Pediatrics 125, 664–672 (2010).

    Article  PubMed  Google Scholar 

  12. Gupta, K., Hooton, T. M. & Stamm, W. E. Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann. Intern. Med. 135, 41–50 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Gupta, K., Sahm, D. F., Mayfield, D. & Stamm, W. E. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis. Clin. Infect. Dis. 33, 89–94 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Foxman, B. Urinary tract infection syndromes. Occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect. Dis. Clin. North Am. 28, 1–13 (2014).

    Article  PubMed  Google Scholar 

  15. Levison, M. E. & Kaye, D. Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative uropathogens. Curr. Infect. Dis. Rep. 15, 109–115 (2013).

    Article  PubMed  Google Scholar 

  16. Ragnarsdottir, B., Lutay, N., Gronberg-Hernandez, J., Koves, B. & Svanborg, C. Genetics of innate immunity and UTI susceptibility. Nat. Rev. Urol. 8, 449–468 (2011).

    Article  PubMed  Google Scholar 

  17. Spencer, J. D., Schwaderer, A. L., Becknell, B., Watson, J. & Hains, D. S. The innate immune response during urinary tract infection and pyelonefritis. Pediatr. Nephrol. 29, 1139–1149 (2015).

    Article  Google Scholar 

  18. Godaly, G., Ambite, I. & Svanborg, C. Innate immunity and genetic determinants of urinary tract infection susceptibility. Curr. Opin. Infect. Dis. 28, 88–96 (2015).

    Article  CAS  PubMed  Google Scholar 

  19. Creagh, E. M. & O'Neill, L. A. TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol. 27, 352–357 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Anand, P. K. et al. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488, 389–393 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805–820 (2010).

    Article  CAS  PubMed  Google Scholar 

  23. Medzhitov, R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1, 135–145 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Kummer, J. A. et al. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J. Histochem. Cytochem. 55, 443–452 (2007).

    Article  CAS  PubMed  Google Scholar 

  25. Hughes, F. M. et al. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation. Am. J. Physiol. Renal Physiol. 306, F299–F308 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Hughes, F. M., Turner, D. P. & Todd Purves, J. The potential repertoire of the innate immune system in the bladder: expression of pattern recognition receptors in the rat bladder and a rat urothelial cell line (MYP3 cells). Int. Urol. Nephrol. 47, 1953–1964 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ting, J. P. Y. et al. The NLR gene family: an official nomenclature. Immunity 28, 285–287 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bürckstümmer, T. et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10, 266–272 (2009).

    Article  PubMed  CAS  Google Scholar 

  29. Jin, T., Perry, A., Smith, P., Jiang, J. & Xiao, T. S. Structure of the absent in melanoma 2 (AIM2) pyrin domain provides insights into the mechanisms of AIM2 autoinhibition and inflammasome assembly. J. Biol. Chem. 288, 13225–13235 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514–518 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rathinam, V. A. K. et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395–402 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jin, T. et al. Structures of the HIN domain: DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity 36, 561–571 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Khare, S. et al. An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity 36, 464–476 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wlodarska, M. et al. NLRP6 inflammasome orchestrates the colonic host–microbial interface by regulating goblet cell mucus secretion. Cell 156, 1045–1059 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vladimer, G. I. et al. The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37, 96–107 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Minkiewicz, J., de Rivero Vaccari, J. P. & Keane, R. W. Human astrocytes express a novel NLRP2 inflammasome. Glia 61, 1113–1121 (2013).

    Article  PubMed  Google Scholar 

  37. Mariathasan, S. et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430, 213–218 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Anand, P. K., Malireddi, R. K. S. & Kanneganti, T. D. Role of the Nlrp3 inflammasome in microbial infection. Front. Microbiol. 2, 12 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10, 417–426 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Guo, H., Callaway, J. B. & Ting, J. P.-Y. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 21, 677–687 (2015). A recent review covering the activation mechanisms of inflammasomes and their role in inflammatory diseases.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).

    Article  CAS  PubMed  Google Scholar 

  42. Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).

    Article  CAS  PubMed  Google Scholar 

  43. Bergsbaken, T., Fink, S. L. & Cookson, B. T. Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 7, 99–109 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fink, S. L. & Cookson, B. T. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907–1916 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gurung, P. et al. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J. Immunol. 192, 1835–1846 (2014).

    Article  CAS  PubMed  Google Scholar 

  46. Man, S. M. et al. Salmonella infection induces recruitment of caspase-8 to the inflammasome to modulate IL-1β production. J. Immunol. 191, 5239–5246 (2013).

    Article  CAS  PubMed  Google Scholar 

  47. Monie, T. P. & Bryant, C. E. Caspase-8 functions as a key mediator of inflammation and pro-IL-1β processing via both canonical and non-canonical pathways. Immunol. Rev. 265, 181–193 (2015).

    Article  CAS  PubMed  Google Scholar 

  48. Dinarello, C. A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27, 519–550 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Brodsky, I. E. & Medzhitov, R. Pyroptosis: macrophage suicide exposes hidden invaders. Curr. Biol. 21, R72–R75 (2011).

    Article  CAS  PubMed  Google Scholar 

  50. He, Y. & Amer, A. O. Microbial modulation of host apoptosis and pyroptosis. Front. Cell. Infect. Microbiol. 4, 1–3 (2014).

    Article  Google Scholar 

  51. Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237–241 (2006).

    Article  CAS  Google Scholar 

  52. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mariathasan, S. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228–232 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Netea, M. G. et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages. Blood 113, 2324–2335 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bauernfeind, F. G. et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183, 787–791 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Gurung, P. et al. Toll or interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF)-mediated caspase-11 protease production integrates toll-like receptor 4 (TLR4) protein- and Nlrp3 inflammasome-mediated host defense against enteropathogens. J. Biol. Chem. 287, 34474–34483 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rathinam, V. A. K. et al. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria. Cell 150, 606–619 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Shi, J. et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187–192 (2014).

    Article  CAS  PubMed  Google Scholar 

  61. Vigano, E. et al. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes. Nat. Commun. 6, 1–13 (2015).

    Article  CAS  Google Scholar 

  62. Casson, C. N. et al. Human caspase-4 mediates noncanonical inflammasome activation against gram-negative bacterial pathogens. Proc. Natl Acad. Sci. USA 112, 6688–6693 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Muñoz-Planillo, R. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38, 1142–1153 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Pétrilli, V. et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 14, 1583–1589 (2007).

    Article  PubMed  CAS  Google Scholar 

  65. Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Lupfer, C. et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat. Immunol. 14, 480–488 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lupfer, C. R. et al. Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection. PLoS Pathog. 10, e1004410 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Shimada, K. et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36, 401–414 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Iyer, S. et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39, 311–323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kuemmerle-Deschner, J. B. CAPS — pathogenesis, presentation and treatment of an autoinflammatory disease. Semin. Immunopathol. 37, 377–385 (2015).

    Article  CAS  PubMed  Google Scholar 

  71. Vandanmagsar, B. et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 17, 179–188 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Stienstra, R. et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc. Natl Acad. Sci. USA 108, 15324–15329 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Vande Walle, L. et al. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature 512, 69–73 (2014).

    Article  PubMed  CAS  Google Scholar 

  74. Abraham, S. N. et al. Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae\Identification and characterization of E. coli type-1 pilus tip adhesion protein. Nature 336, 682–684 (1988).

    Article  CAS  PubMed  Google Scholar 

  75. Martinez, J. J., Mulvey, M. A., Schilling, J. D., Pinkner, J. S. & Hultgren, S. J. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J. 19, 2803–2812 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Fukushi, Y., Orikasa, S. & Kagayama, M. An electron microscopic study of the interaction between vesical epitherlium and E. Coli. Invest. Urol. 17, 61–68 (1979).

    CAS  PubMed  Google Scholar 

  77. Mulvey, M. A. et al. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282, 1494–1497 (1998).

    Article  CAS  PubMed  Google Scholar 

  78. Song, J. et al. TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. Proc. Natl Acad. Sci. USA 106, 14966–14971 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Anderson, G. G. et al. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301, 105–107 (2003).

    Article  CAS  PubMed  Google Scholar 

  80. Anderson, G. G., Dodson, K. W., Hooton, T. M. & Hultgren, S. J. Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis. Trends Microbiol. 12, 424–430 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Mysorekar, I. U. & Hultgren, S. J. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc. Natl Acad. Sci. USA 103, 14170–14175 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Abraham, S. N. & Miao, Y. The nature of immune responses to urinary tract infections. Nat. Rev. Immunol. 15, 655–663 (2015). A recent review on the current knowledge of innate immune responses to UTIs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schilling, J. D., Martin, S. M., Hung, C. S., Lorenz, R. G. & Hultgren, S. J. Toll-like receptor 4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic Escherichia coli. Proc. Natl Acad. Sci. USA 100, 4203–4208 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Schilling, J. D., Mulvey, M. A., Vincent, C. D., Lorenz, R. G. & Hultgren, S. J. Bacterial invasion augments epithelial cytokine responses to Escherichia coli through a lipopolysaccharide-dependent mechanism. J. Immunol. 166, 1148–1155 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Hagberg, L. et al. Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect. Immun. 46, 839–844 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Andersen-Nissen, E. et al. Cutting edge: Tlr5−/− mice are more susceptible to Escherichia coli urinary tract infection. J. Immunol. 178, 4717–4720 (2007).

    Article  CAS  PubMed  Google Scholar 

  87. Zhang, D. et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303, 1522–1526 (2004).

    Article  CAS  PubMed  Google Scholar 

  88. Frendéus, B. et al. Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J. Exp. Med. 192, 881–890 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Yin, X. et al. Association of Toll-like receptor 4 gene polymorphism and expression with urinary tract infection types in adults. PLoS ONE 5, e14223 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hawn, T. R. et al. Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women. PLoS ONE 4, e8300 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Zhang, X. et al. Enterohemorrhagic Escherichia coli specific enterohemolysin induced IL-1beta in human macrophages and EHEC-induced IL-1beta required activation of NLRP3 inflammasome. PLoS ONE 7, e50288 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Schaale, K. et al. Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli. Mucosal Immunol. 9, 124–136 (2015). This paper demonstrates the activation of the inflammasome and cell death by uropathogenic E. coli.

    Article  PubMed  CAS  Google Scholar 

  93. Coll, R. C. et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21, 248–255 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Mabbett, A. N. et al. Virulence properties of asymptomatic bacteriuria Escherichia coli. Int. J. Med. Microbiol. 299, 53–63 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Smith, Y. C., Rasmussen, S. B., Grande, K. K., Conran, R. M. & O'Brien, A. D. Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice. Infect. Immun. 76, 2978–2990 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Waldhuber, A., Puthia, M. & Wieser, A. Uropathogenic Escherichia coli strain CFT073 disrupts NLRP3 inflammasome activation. J. Clin. Invest. 126, 2425–2436 (2016). A recent paper revealing the inhibition of the NLRP3 inflammasome by a UPEC virulence factor, TcpC.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Schubert, S. et al. Prevalence and phylogenetic history of the TcpC virulence determinant in Escherichia coli. Int. J. Med. Microbiol. 300, 429–434 (2010).

    Article  CAS  PubMed  Google Scholar 

  98. Cirl, C. et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat. Med. 14, 399–406 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. Nagamatsu, K. et al. Dysregulation of Escherichia coli α-hemolysin expression alters the course of acute and persistent urinary tract infection. Proc. Natl Acad. Sci. USA 112, E871–E880 (2015). This paper highlights the activation of caspase-1-dependent pyroptosis by UPEC virulence factor, α-haemolysin. Additionally, it demonstrates increased urothelium exfoliation and reduced murine bladder infection upon α-haemolysin overexpression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Mulvey, M. A., Schilling, J. D., Martinez, J. J. & Hultgren, S. J. Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. Proc. Natl Acad. Sci. USA 97, 8829–8835 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Dhakal, B. K. & Mulvey, M. A. The UPEC pore-forming toxin α-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways. Cell Host Microbe 11, 58–69 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Schwartz, D. J., Conover, M. S., Hannan, T. J. & Hultgren, S. J. Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection. PLoS Pathog. 11, 1–12 (2015). This paper reveals the importance of reintroduction of bacteria (superinfection) and the possible involvement of caspases in the development of recurrent infection following acute UTI.

    Google Scholar 

  104. Klumpp, D. J. et al. Uropathogenic Escherichia coli induces extrinsic and intrinsic cascades to initiate urothelial apoptosis. Infect. Immun. 74, 5106–5113 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Levine, B., Mizushima, N. & Virgin, H. W. Autophagy in immunity and inflammation. Nature 469, 323–335 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Deretic, V., Saitoh, T. & Akira, S. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13, 722–737 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kuballa, P., Nolte, W. M., Castoreno, A. B. & Xavier, R. J. Autophagy and the immune system. Annu. Rev. Immunol. 30, 611–646 (2012).

    Article  CAS  PubMed  Google Scholar 

  108. Anand, P. K. et al. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J. Biol. Chem. 286, 42981–42991 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Feng, Y., He, D., Yao, Z. & Klionsky, D. J. The machinery of macroautophagy. Cell Res. 24, 24–41 (2014).

    Article  CAS  PubMed  Google Scholar 

  110. Ryter, S. W. & Choi, A. M. K. Autophagy: an integral component of the mammalian stress response. J. Biochem. Pharmacol. Res. 1, 176–188 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Plantinga, T. S., Joosten, L. A. B. & Netea, M. G. ATG16L1 polymorphisms are associated with NOD2-induced hyperinflammation. Autophagy 7, 1074–1075 (2011).

    Article  CAS  PubMed  Google Scholar 

  112. Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39, 207–211 (2007).

    Article  CAS  PubMed  Google Scholar 

  113. Saitoh, T. et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1 beta production. Nature 456, 264–268 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Symington, J. W. et al. ATG16L1 deficiency in macrophages drives clearance of uropathogenic E. coli in an IL-1β-dependent manner. Mucosal Immunol. 8, 1–12 (2015). This paper investigates the role of autophagy in UPEC infection, and reveals protection against UPEC in the absence of autophagic protein ATG16L1.

    Article  CAS  Google Scholar 

  115. Wang, C. et al. Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo. Proc. Natl Acad. Sci. USA 109, 11008–11013 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Shi, C.-S. et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol. 13, 255–263 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Harris, J. et al. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J. Biol. Chem. 286, 9587–9597 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lassen, K. G. et al. Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc. Natl Acad. Sci. USA 111, 7741–7746 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Schuchat, A. Group B streptococcus. Lancet 353, 51–56 (1999).

    Article  CAS  PubMed  Google Scholar 

  120. Skoff, T. H. et al. Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990–2007. Clin. Infect. Dis. 49, 85–92 (2009).

    Article  PubMed  Google Scholar 

  121. Ulett, G. C., Maclean, K. H., Nekkalapu, S., Cleveland, J. L. & Adderson, E. E. Mechanisms of group B streptococcal-induced apoptosis of murine macrophages. J. Immunol. 175, 2555–2562 (2005).

    Article  CAS  PubMed  Google Scholar 

  122. Ulett, G. C. et al. Group B Streptococcus (GBS) urinary tract infection involves binding of GBS to bladder uroepithelium and potent but GBS-specific induction of interleukin 1alpha. J. Infect. Dis. 201, 866–870 (2010). This paper examines the production of cytokines IL-1α and IL-1β following attachment of Group B Streptococcus to the bladder epithelial cells.

    Article  PubMed  Google Scholar 

  123. Zaleznik, D. F. et al. Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups. Clin. Infect. Dis. 30, 276–281 (2000).

    Article  CAS  PubMed  Google Scholar 

  124. Muñoz, P. et al. Group B Streptococcus: a cause of urinary tract infection in nonpregnant adults. Clin. Infect. Dis. 14, 492–496 (1992).

    Article  PubMed  Google Scholar 

  125. Falagas, M. E., Rosmarakis, E. S., Avramopoulos, I. & Vakalis, N. Streptococcus agalactiae infections in non-pregnant adults: single center experience of a growing clinical problem. Med. Sci. Monit. 12, CR447–CR451 (2006).

    PubMed  Google Scholar 

  126. Williams, P. A. et al. Production of tumor necrosis factor by human cells in vitro and in vivo, induced by group B streptococci. J. Pediatr. 123, 292–300 (1993).

    Article  CAS  PubMed  Google Scholar 

  127. Mancuso, G. et al. Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria. J. Immunol. 178, 3126–3133 (2007).

    Article  CAS  PubMed  Google Scholar 

  128. Gross, O. et al. Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36, 388–400 (2012).

    Article  CAS  PubMed  Google Scholar 

  129. Billips, B. K. et al. Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli. Infect. Immun. 75, 5353–5360 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Costa, A. et al. Activation of the NLRP3 inflammasome by group B streptococci. J. Immunol. 188, 1953–1960 (2012). This paper investigates the activation of the NLRP3 inflammasome by Group B Streptroccocus via its virulence factor β-haemolysin.

    Article  CAS  PubMed  Google Scholar 

  131. Biondo, C. et al. The interleukin-1β/CXCL1/2/neutrophil axis mediates host protection against group B streptococcal infection. Infect. Immun. 82, 4508–4517 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Charrel-Dennis, M. et al. TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA. Cell Host Microbe 4, 543–554 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Gupta, R. et al. RNA and beta;-hemolysin of group B streptococcus induce interleukin-1β (IL-1β) by activating NLRP3 inflammasomes in mouse macrophages. J. Biol. Chem. 289, 13701–13705 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Li, J. et al. DDX19A senses viral RNA and mediates NLRP3-dependent inflammasome activation. J. Immunol. 195, 5732–5749 (2015).

    Article  CAS  PubMed  Google Scholar 

  135. Mitoma, H. et al. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 39, 123–135 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Amna, M. A., Chazan, B., Raz, R., Edelstein, H. & Colodner, R. Risk factors for non-Escherichia coli community-acquired bacteriuria. Infection 41, 473–477 (2013).

    Article  CAS  PubMed  Google Scholar 

  137. Melzer, M. & Welch, C. Outcomes in UK patients with hospital-acquired bacteraemia and the risk of catheter-associated urinary tract infections. Postgrad. Med. J. 89, 329–334 (2013).

    Article  PubMed  Google Scholar 

  138. Mittal, R., Aggarwal, S., Sharma, S., Chhibber, S. & Harjai, K. Urinary tract infections caused by Pseudomonas aeruginosa: a minireview. J. Infect. Public Health 2, 101–111 (2009).

    Article  PubMed  Google Scholar 

  139. Mah, T. F. et al. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426, 306–310 (2003).

    Article  CAS  PubMed  Google Scholar 

  140. Mah, T. F. C. & O'Toole, G. A. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9, 34–39 (2001).

    Article  CAS  PubMed  Google Scholar 

  141. Costerton, J. W., Stewart, P. S. & Greenberg, E. P. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318–1322 (1999).

    Article  CAS  PubMed  Google Scholar 

  142. Poyet, J. L. et al. Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J. Biol. Chem. 276, 28309–28313 (2001).

    Article  CAS  PubMed  Google Scholar 

  143. Molofsky, A. B. et al. Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J. Cell Biol. 173, 1093–1104 (2006).

    Article  Google Scholar 

  144. Ren, T., Zamboni, D. S., Roy, C. R., Dietrich, W. F. & Vance, R. E. Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog. 2, e18 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Franchi, L. et al. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nat. Immunol. 7, 576–582 (2006).

    Article  CAS  PubMed  Google Scholar 

  146. Miao, E. A. et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin-1β via Ipaf. Nat. Immunol. 7, 569–575 (2006).

    Article  CAS  PubMed  Google Scholar 

  147. Zamboni, D. S. et al. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat. Immunol. 7, 318–325 (2006).

    Article  CAS  PubMed  Google Scholar 

  148. Suzuki, T. et al. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 3, 1082–1091 (2007).

    Article  CAS  Google Scholar 

  149. Franchi, L. et al. Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation. Eur. J. Immunol. 37, 3030–3039 (2007).

    Article  CAS  PubMed  Google Scholar 

  150. Zhao, Y. et al. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature 477, 596–600 (2011).

    Article  CAS  PubMed  Google Scholar 

  151. Kofoed, E. M. & Vance, R. E. Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature 477, 592–595 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Lightfield, K. L. et al. Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. Nat. Immunol. 9, 1171–1178 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Miao, E. A. et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc. Natl Acad. Sci. USA 107, 3076–3080 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Sutterwala, F. S. et al. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 204, 3235–3245 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Lindestam Arlehamn, C. S. & Evans, T. J. Pseudomonas aeruginosa pilin activates the inflammasome. Cell. Microbiol. 13, 388–401 (2011).

    Article  PubMed Central  CAS  Google Scholar 

  156. Cohen, T. S. & Prince, A. S. Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia. J. Clin. Invest. 123, 1630–1637 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Schultz, M. J. et al. Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L285–L290 (2002).

    Article  CAS  PubMed  Google Scholar 

  158. Mittal, R., Sharma, S., Chhibber, S. & Harjai, K. Evaluation of tumour necrosis factor-alpha and interleukin-1beta in an experimental pyelonephritis model induced with planktonic and biofilms cells of Pseudomonas aeruginosa. Can. J. Infect. Dis. Med. Microbiol. 20, 35–42 (2009). This paper suggests a role for neutrophils in P. aeruginosa -induced pyelonephritis.

    Article  Google Scholar 

  159. Sabharwal, N., Chhibber, S. & Harjai, K. New possibility for providing protection against urinary tract infection caused by Pseudomonas aeruginosa by non-adjuvanted flagellin 'b' induced immunity. Immunol. Lett. 162, 229–238 (2014).

    Article  CAS  PubMed  Google Scholar 

  160. Bhat, R. G., Katy, T. A. & Place, F. C. Pediatric urinary tract infections. Emerg. Med. Clin. North Am. 29, 637–653 (2011).

    Article  PubMed  Google Scholar 

  161. Lin, K. Y. et al. Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection. Pediatr. Nephrol. 18, 362–365 (2003).

    Article  PubMed  Google Scholar 

  162. Colgan, R., Williams, M. & Johnson, J. R. Diagnosis and treatment of acute pyelonephritis in women. Am. Fam. Physician 84, 519–526 (2011).

    PubMed  Google Scholar 

  163. Sheu, J.-N. et al. Urine interleukin-1beta in children with acute pyelonephritis and renal scarring. Nephrology (Carlton). 12, 487–493 (2007). This paper examines the correlation between IL-1β levels in the urine and acute polynephritis.

    Article  CAS  PubMed  Google Scholar 

  164. Mahyar, A. et al. Are serum procalcitonin and interleukin-1 beta suitable markers for diagnosis of acute pyelonephritis in children? Prague Med. Rep. 115, 16–23 (2014).

    Article  CAS  PubMed  Google Scholar 

  165. Kassir, K. et al. Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact. Clin. Diagn. Lab. Immunol. 8, 1060–1063 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Gürgöze, M. K. et al. Proinflammatory cytokines and procalcitonin in children with acute pyelonephritis. Pediatr. Nephrol. 20, 1445–1448 (2005).

    Article  PubMed  Google Scholar 

  167. Khalil, A. et al. Cytokine gene expression during experimental Escherichia coli pyelonephritis in mice. J. Urol. 158, 1576–1580 (1997). This paper highlights the production of IL-1β in an experimental model of acute pyelonephritis.

    Article  CAS  PubMed  Google Scholar 

  168. Hertting, O. et al. Enhanced chemokine response in experimental acute Escherichia coli pyelonephritis in IL-1 beta-deficient mice. Clin. Exp. Immunol. 131, 225–233 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Netea, M. G. et al. IL-1β processing in host defense: beyond the inflammasomes. PLoS Pathog. 6, e1000661 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Lukens, J. R. et al. Critical role for inflammasome-independent IL-1β production in osteomyelitis. Proc. Natl Acad. Sci. USA 111, 1066–1071 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Hughes, F. et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J. Urol. 195, 1598–1605 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Wright, K. J., Seed, P. C. & Hultgren, S. J. Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization. Infect. Immun. 73, 7657–7668 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Rama, G., Chhina, D. K., Chhina, R. S. & Sharma, S. Urinary tract infections — microbial virulence determinants and reactive oxygen species. Comp. Immunol. Microbiol. Infect. Dis. 28, 339–349 (2005).

    Article  CAS  PubMed  Google Scholar 

  174. Hughes, F. M. Jr et al. The NACHT, NRR and PYD domains-containing protein 3 (NLRP3) inflammasome mediates inflammation and voiding dysfunction in a lipopolysaccharide-induced rat model of cystitis. J. Clin. Cell. Immunol. 7, 396 (2016). This paper explores a role for the NLRP3 inflammasome in LPS-mediated responses in the bladder.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Malley, S. E. & Vizzard, M. A. Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis. Physiol. Genomics 9, 5–13 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

L.T. is now an employee of GlaxoSmithKline, UK. T.M. was supported by the Deutsche Forschungsgemeinschaft (DFG) grant MI471/6-1. Work in the laboratory of P.A. is supported by funds from The Wellcome Trust (108248/Z/15/Z), The Royal Society (RG150535) and core funds from Imperial College London.

Author information

Authors and Affiliations

  1. Infectious Diseases and Immunity, Imperial College London, The Commonwealth Building, Du Cane Road, London, W12 0NN, UK

    Claire Hamilton, Lionel Tan & Paras K. Anand

  2. Institute of Medical Microbiology and Hygiene, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, Mannheim, 68167, Germany

    Thomas Miethke

Authors
  1. Claire Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lionel Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Miethke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paras K. Anand
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.K.A., C.H., and L.T. researched data for the article. P.K.A. and C.H. wrote the manuscript. P.K.A. and T.M. took part in discussions of content. All authors reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Paras K. Anand.

Ethics declarations

Competing interests

L.T. declares employment with GlaxoSmithKline, UK. The other authors declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamilton, C., Tan, L., Miethke, T. et al. Immunity to uropathogens: the emerging roles of inflammasomes. Nat Rev Urol 14, 284–295 (2017). https://doi.org/10.1038/nrurol.2017.25

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2017.25

This article is cited by

Search

Advanced 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