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Mucosal immunity to pathogenic intestinal bacteria

Nature Reviews Immunology volume 16, pages 135–148 (2016)Cite this article

Subjects

Key Points

  • Pathogens have to overcome colonization resistance by the microbiota to colonize the gut and to cause disease.

  • The microbiota modulates the immune system to limit pathogen colonization but also inadvertently helps certain pathogens to colonize, for example, by making electron acceptors and carbon sources available.

  • Pathogens are quickly sensed by innate pattern-recognition receptors (for example, Toll-like receptors (TLRs) and NOD-like receptors (NLRs)) on various cell types, which results in a pro-inflammatory response, for example, activation of the inflammasome.

  • Activation of innate receptors triggers an inflammatory response (for example, the interleukin-23–T helper 17 cell axis) that for some pathogens initially promotes colonization but ultimately results in clearance of pathogens.

  • Recruitment of high numbers of neutrophils to the site of infection is a hallmark of inflammatory diarrhoea and is generally beneficial to the host as it controls pathogens.

  • Secretory IgA antibodies are important to maintain the mucosal barrier and to protect against pathogens, for example, Vibrio cholerae or Salmonella spp.

Abstract

The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria.

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Figure 1: Pathogens exploit the microbiota to colonize the gut.
Figure 2: Commensal microorganisms modulate intestinal immunity.
Figure 3: Activation of NLRs in the gut.
Figure 4: Antimicrobial responses induced by IL-22.
Figure 5: General overview of mucosal immunity to intestinal pathogens and commensal microorganisms.

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Acknowledgements

Work in the M.R. laboratory is supported by Public Health Service Grants AI083663, AI101784, AI105374, AI114625, and DK058057. M.R. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. A.P.L. was funded by a UC MEXUS-CONACYT award.

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  1. Department of Microbiology and Molecular Genetics, and Institute for Immunology, University of California Irvine School of Medicine, Irvine, 92697-4025, California, USA

    Araceli Perez-Lopez, Judith Behnsen, Sean-Paul Nuccio & Manuela Raffatellu

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  1. Araceli Perez-Lopez
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Correspondence to Manuela Raffatellu.

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Perez-Lopez, A., Behnsen, J., Nuccio, SP. et al. Mucosal immunity to pathogenic intestinal bacteria. Nat Rev Immunol 16, 135–148 (2016). https://doi.org/10.1038/nri.2015.17

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