Research ArticleMUCOSAL IMMUNOLOGY

Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution

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Science Immunology  07 Feb 2020:
Vol. 5, Issue 44, eaay3254
DOI: 10.1126/sciimmunol.aay3254

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Managing microbiota to a T

Mucosal surfaces in teleost fish harbor B cells that produce IgT, a secretory mucosal immunoglobulin. To investigate how IgT influences gill microbiota composition and resistance to infection, Xu et al. developed an efficient technique for temporarily depleting IgT-producing B cells in rainbow trout. Acute induction of IgT deficiency in trout led to dysbiosis of commensal gill microbiota, inflammation, tissue damage, and impaired resistance to infection by a mucosal parasite. The gill pathology triggered by loss of IgT was reversible after IgT levels recovered to the normal range. These findings demonstrate that the mucosal immunoglobulin species in both teleost fish (IgT) and mammals (mostly IgA) play evolutionarily conserved roles in the maintenance of healthy commensal microbiota communities and control of pathogens.

Abstract

Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome homeostasis. To address this central question, we used a primitive vertebrate species (rainbow trout) in which we temporarily depleted its mucosal Ig (sIgT). Fish devoid of sIgT became highly susceptible to a mucosal parasite and failed to develop compensatory IgM responses against it. IgT depletion also induced a profound dysbiosis marked by the loss of sIgT-coated beneficial taxa, expansion of pathobionts, tissue damage, and inflammation. Restitution of sIgT levels in IgT-depleted fish led to a reversal of microbial translocation and tissue damage, as well as to restoration of microbiome homeostasis. Our findings indicate that specialization of sIgs in pathogen and microbiota control occurred concurrently early in evolution, thus revealing primordially conserved principles under which primitive and modern sIgs operate in the control of microbes at mucosal surfaces.

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