The immune response to infection in the bladder

Abstract

The bladder is continuously protected by passive defences such as a mucus layer, antimicrobial peptides and secretory immunoglobulins; however, these defences are occasionally overcome by invading bacteria that can induce a strong host inflammatory response in the bladder. The urothelium and resident immune cells produce additional defence molecules, cytokines and chemokines, which recruit inflammatory cells to the infected tissue. Resident and recruited immune cells act together to eradicate bacteria from the bladder and to develop lasting immune memory against infection. However, urinary tract infection (UTI) is commonly recurrent, suggesting that the induction of a memory response in the bladder is inadequate to prevent reinfection. Additionally, infection seems to induce long-lasting changes in the urothelium, which can render the tissue more susceptible to future infection. The innate immune response is well-studied in the field of UTI, but considerably less is known about how adaptive immunity develops and how repair mechanisms restore bladder homeostasis following infection. Furthermore, data demonstrate that sex-based differences in immunity affect resolution and infection can lead to tissue remodelling in the bladder following resolution of UTI. To combat the rise in antimicrobial resistance, innovative therapeutic approaches to bladder infection are currently in development. Improving our understanding of how the bladder responds to infection will support the development of improved treatments for UTI, particularly for those at risk of recurrent infection.

Key points

  • The bladder contains constitutive passive defences, such as mucus and immunoglobulins, to protect it against colonization.

  • Robust cytokine expression and inflammatory cell infiltration into the bladder during urinary tract infection are dependent on bacterial species and sex.

  • Uropathogenic Escherichia coli induces a non-sterilizing adaptive immune response in the bladder.

  • Uropathogenic Escherichia coli causes long-lasting changes in the bladder urothelium, conferring resistance or increased susceptibility to subsequent infections depending on the outcomes of the first infection.

  • Vaccines and other non-antibiotic-based therapies in development might provide therapeutic relief to those suffering from recurrent or chronic urinary tract infection.

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Fig. 1: Designating bacterial prostatitis as a UTI.
Fig. 2: Structure of the glycosaminoglycan layer of the bladder wall.
Fig. 3: Constitutive and induced immune responses in the bladder.

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Acknowledgements

We thank M. Rousseau for critical reading of the manuscript. L.L.M. is part of the Pasteur-Paris University (PPU) International PhD Program, which received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 665807 and from the Labex Milieu Intérieur (ANR-10-LABX-69-01). We would also like to acknowledge funding from the Agence Nationale de la Recherché (French National Research Agency) grant number ANR-17-CE17-0014 for supporting our work on urinary tract infection and host responses.

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Lacerda Mariano, L., Ingersoll, M.A. The immune response to infection in the bladder. Nat Rev Urol 17, 439–458 (2020). https://doi.org/10.1038/s41585-020-0350-8

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