Immune Defenses in the Urinary Tract

Overview

Journal Trends Immunol

Specialty Allergy & Immunology

Date 2023 Aug 17

PMID 37591712

Authors

Hunter W Kuhn

Teri N Hreha

David A Hunstad

Affiliations

Soon will be listed here.

Abstract

Recent advances in preclinical modeling of urinary tract infections (UTIs) have enabled the identification of key facets of the host response that influence pathogen clearance and tissue damage. Here, we review new insights into the functions of neutrophils, macrophages, and antimicrobial peptides in innate control of uropathogens and in mammalian infection-related tissue injury and repair. We also discuss novel functions for renal epithelial cells in innate antimicrobial defense. In addition, epigenetic modifications during bacterial cystitis have been implicated in bladder remodeling, conveying susceptibility to recurrent UTI. In total, contemporary work in this arena has better defined host processes that shape UTI susceptibility and severity and might inform the development of novel preventive and therapeutic approaches for acute and recurrent UTI.

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References

Ajibade A, Wang Q, Cui J, Zou J, Xia X, Wang M . TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils. Immunity. 2012; 36(1):43-54. PMC: 3750978. DOI: 10.1016/j.immuni.2011.12.010. View

Taneja R, Sharma A, Hallett M, Findlay G, Morris M . Immature circulating neutrophils in sepsis have impaired phagocytosis and calcium signaling. Shock. 2008; 30(6):618-22. DOI: 10.1097/SHK.0b013e318173ef9c. View

Becknell B, Schwaderer A, Hains D, Spencer J . Amplifying renal immunity: the role of antimicrobial peptides in pyelonephritis. Nat Rev Nephrol. 2015; 11(11):642-55. DOI: 10.1038/nrneph.2015.105. View

Gilbert N, OBrien V, Waller C, Batourina E, Mendelsohn C, Lewis A . Exposures Alter Bladder Gene Expression and Augment Uropathogenic Urinary Tract Infection in Mice. Front Cell Infect Microbiol. 2022; 12:909799. PMC: 9245024. DOI: 10.3389/fcimb.2022.909799. View

Paragas N, Kulkarni R, Werth M, Schmidt-Ott K, Forster C, Deng R . α-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest. 2014; 124(7):2963-76. PMC: 4071397. DOI: 10.1172/JCI71630. View

Olson P, McLellan L, Hreha T, Liu A, Briden K, Hruska K . Androgen exposure potentiates formation of intratubular communities and renal abscesses by Escherichia coli. Kidney Int. 2018; 94(3):502-513. PMC: 6109434. DOI: 10.1016/j.kint.2018.04.023. View

Geerlings S . Urinary tract infections in patients with diabetes mellitus: epidemiology, pathogenesis and treatment. Int J Antimicrob Agents. 2007; 31 Suppl 1:S54-7. DOI: 10.1016/j.ijantimicag.2007.07.042. View

Hagberg L, Hull R, Hull S, McGhee J, Michalek S, Svanborg Eden C . Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect Immun. 1984; 46(3):839-44. PMC: 261623. DOI: 10.1128/iai.46.3.839-844.1984. View

Lacerda Mariano L, Rousseau M, Varet H, Legendre R, Gentek R, Saenz Coronilla J . Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder. Sci Adv. 2020; 6(48). PMC: 7688323. DOI: 10.1126/sciadv.abc5739. View

10.

Nahrendorf M, Swirski F . Abandoning M1/M2 for a Network Model of Macrophage Function. Circ Res. 2016; 119(3):414-7. PMC: 4965179. DOI: 10.1161/CIRCRESAHA.116.309194. View

11.

Shahin R, Engberg I, Hagberg L, Svanborg Eden C . Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J Immunol. 1987; 138(10):3475-80. View

12.

Nagamatsu K, Hannan T, Guest R, Kostakioti M, Hadjifrangiskou M, Binkley J . Dysregulation of Escherichia coli α-hemolysin expression alters the course of acute and persistent urinary tract infection. Proc Natl Acad Sci U S A. 2015; 112(8):E871-80. PMC: 4345586. DOI: 10.1073/pnas.1500374112. View

13.

Wu J, Bao C, Reinhardt R, Abraham S . Local induction of bladder Th1 responses to combat urinary tract infections. Proc Natl Acad Sci U S A. 2021; 118(10). PMC: 7958421. DOI: 10.1073/pnas.2026461118. View

14.

Lehmann J, Retz M, Harder J, Krams M, Kellner U, Hartmann J . Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection. BMC Infect Dis. 2002; 2:20. PMC: 128826. DOI: 10.1186/1471-2334-2-20. View

15.

Song J, Abraham S . TLR-mediated immune responses in the urinary tract. Curr Opin Microbiol. 2008; 11(1):66-73. PMC: 2775047. DOI: 10.1016/j.mib.2007.12.001. View

16.

Nielubowicz G, Mobley H . Host-pathogen interactions in urinary tract infection. Nat Rev Urol. 2010; 7(8):430-41. DOI: 10.1038/nrurol.2010.101. View

17.

Davies L, Jenkins S, Allen J, Taylor P . Tissue-resident macrophages. Nat Immunol. 2013; 14(10):986-95. PMC: 4045180. DOI: 10.1038/ni.2705. View

18.

Carey A, Sullivan M, Duell B, Crossman D, Chattopadhyay D, Brooks A . Uropathogenic Escherichia coli Engages CD14-Dependent Signaling to Enable Bladder-Macrophage-Dependent Control of Acute Urinary Tract Infection. J Infect Dis. 2015; 213(4):659-68. DOI: 10.1093/infdis/jiv424. View

19.

Flores-Mireles A, Walker J, Caparon M, Hultgren S . Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5):269-84. PMC: 4457377. DOI: 10.1038/nrmicro3432. View

20.

Zychlinsky Scharff A, Rousseau M, Lacerda Mariano L, Canton T, Consiglio C, Albert M . Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection. JCI Insight. 2019; 5. PMC: 6629110. DOI: 10.1172/jci.insight.122998. View