Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

By Gregory F. Sonnenberg, L. Monticelli, T. Alenghat, Thomas C. Fung, N. Hutnick, J. Kunisawa, Naoko Shibata, Stephanie Grunberg, Rohini Sinha, Adam M. Zahm and 14 more. Science, 2012

695 citations recorded by the source corpus.

Protecting Against a Barrier Breach In order to coexist peacefully, a “firewall” exists that keeps the commensal bacteria that reside in our intestines and associated lymphoid tissue contained. Several diseases and infections, however, lead to a breach in this barrier, which leads to chronic inflammation and pathology. Sonnenberg et al. (p. 1321) found that in mice, innate lymphoid cells (ILCs) are critically important for the anatomical containment of commensal bacteria in an interleukin-22 (IL-22)–dependent manner. ILC depletion or blockade of IL-22 led to loss of bacterial containment and systemic inflammation. Lymphocytes prevent bacteria from spreading beyond gut-associated lymphoid tissues and causing systemic inflammation. The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)–producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn’s disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.

Subfields: Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/45f0f902e9c2cc296e6080d85a7579b763b27165

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In Immunology

1. O. Harrison
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Citations in the corpus

• Homeostatic immunity and the microbiota (2017, positive): “Production of IL-22 by ILC can promote the containment of specific members of the microbiota community residing in mucosal lymphoid structures, such as bacteria of the Alcaligenes genus (Qiu et al., 2013; Sonnenberg et al., 2012).”
• Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “All rights reserved antimicrobial proteins (RegIII b, RegIIIg, S100A8, and S100A9), which are integral for compartmentalization of gut bacteria within the gastrointestinal tract (106).”