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Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis
The FUT2 α1,2fucosyltransferase contributes to the synthesis of fucosylated glycans used as attachment factors by several pathogens, including noroviruses and rotaviruses, that can induce life-threatening gastroenteritis in young children. FUT2 genetic polymorphisms impairing fucosylation are strong...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008897/ https://www.ncbi.nlm.nih.gov/pubmed/36922975 http://dx.doi.org/10.3389/fmicb.2023.1123803 |
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author | Godefroy, Emmanuelle Barbé, Laure Le Moullac-Vaidye, Béatrice Rocher, Jézabel Breiman, Adrien Leuillet, Sébastien Mariat, Denis Chatel, Jean-Marc Ruvoën-Clouet, Nathalie Carton, Thomas Jotereau, Francine Le Pendu, Jacques |
author_facet | Godefroy, Emmanuelle Barbé, Laure Le Moullac-Vaidye, Béatrice Rocher, Jézabel Breiman, Adrien Leuillet, Sébastien Mariat, Denis Chatel, Jean-Marc Ruvoën-Clouet, Nathalie Carton, Thomas Jotereau, Francine Le Pendu, Jacques |
author_sort | Godefroy, Emmanuelle |
collection | PubMed |
description | The FUT2 α1,2fucosyltransferase contributes to the synthesis of fucosylated glycans used as attachment factors by several pathogens, including noroviruses and rotaviruses, that can induce life-threatening gastroenteritis in young children. FUT2 genetic polymorphisms impairing fucosylation are strongly associated with resistance to dominant strains of both noroviruses and rotaviruses. Interestingly, the wild-type allele associated with viral gastroenteritis susceptibility inversely appears to be protective against several inflammatory or autoimmune diseases for yet unclear reasons, although a FUT2 influence on microbiota composition has been observed. Here, we studied a cohort of young healthy adults and showed that the wild-type FUT2 allele was associated with the presence of anti-RVA antibodies, either neutralizing antibodies or serum IgA, confirming its association with the risk of RVA gastroenteritis. Strikingly, it was also associated with the frequency of gut microbiota-induced regulatory T cells (Tregs), so-called DP8α Tregs, albeit only in individuals who had anti-RVA neutralizing antibodies or high titers of anti-RVA IgAs. DP8α Tregs specifically recognize the human symbiont Faecalibacterium prausnitzii, which strongly supports their induction by this anti-inflammatory bacterium. The proportion of F. prausnitzii in feces was also associated with the FUT2 wild-type allele. These observations link the FUT2 genotype with the risk of RVA gastroenteritis, the microbiota and microbiota-induced DP8α Treg cells, suggesting that the anti-RVA immune response might involve an induction/expansion of these T lymphocytes later providing a balanced immunological state that confers protection against inflammatory diseases. |
format | Online Article Text |
id | pubmed-10008897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100088972023-03-14 Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis Godefroy, Emmanuelle Barbé, Laure Le Moullac-Vaidye, Béatrice Rocher, Jézabel Breiman, Adrien Leuillet, Sébastien Mariat, Denis Chatel, Jean-Marc Ruvoën-Clouet, Nathalie Carton, Thomas Jotereau, Francine Le Pendu, Jacques Front Microbiol Microbiology The FUT2 α1,2fucosyltransferase contributes to the synthesis of fucosylated glycans used as attachment factors by several pathogens, including noroviruses and rotaviruses, that can induce life-threatening gastroenteritis in young children. FUT2 genetic polymorphisms impairing fucosylation are strongly associated with resistance to dominant strains of both noroviruses and rotaviruses. Interestingly, the wild-type allele associated with viral gastroenteritis susceptibility inversely appears to be protective against several inflammatory or autoimmune diseases for yet unclear reasons, although a FUT2 influence on microbiota composition has been observed. Here, we studied a cohort of young healthy adults and showed that the wild-type FUT2 allele was associated with the presence of anti-RVA antibodies, either neutralizing antibodies or serum IgA, confirming its association with the risk of RVA gastroenteritis. Strikingly, it was also associated with the frequency of gut microbiota-induced regulatory T cells (Tregs), so-called DP8α Tregs, albeit only in individuals who had anti-RVA neutralizing antibodies or high titers of anti-RVA IgAs. DP8α Tregs specifically recognize the human symbiont Faecalibacterium prausnitzii, which strongly supports their induction by this anti-inflammatory bacterium. The proportion of F. prausnitzii in feces was also associated with the FUT2 wild-type allele. These observations link the FUT2 genotype with the risk of RVA gastroenteritis, the microbiota and microbiota-induced DP8α Treg cells, suggesting that the anti-RVA immune response might involve an induction/expansion of these T lymphocytes later providing a balanced immunological state that confers protection against inflammatory diseases. Frontiers Media S.A. 2023-02-27 /pmc/articles/PMC10008897/ /pubmed/36922975 http://dx.doi.org/10.3389/fmicb.2023.1123803 Text en Copyright © 2023 Godefroy, Barbé, Le Moullac-Vaidye, Rocher, Breiman, Leuillet, Mariat, Chatel, Ruvoën-Clouet, Carton, Jotereau and Le Pendu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Godefroy, Emmanuelle Barbé, Laure Le Moullac-Vaidye, Béatrice Rocher, Jézabel Breiman, Adrien Leuillet, Sébastien Mariat, Denis Chatel, Jean-Marc Ruvoën-Clouet, Nathalie Carton, Thomas Jotereau, Francine Le Pendu, Jacques Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title | Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title_full | Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title_fullStr | Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title_full_unstemmed | Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title_short | Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis |
title_sort | microbiota-induced regulatory t cells associate with fut2-dependent susceptibility to rotavirus gastroenteritis |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008897/ https://www.ncbi.nlm.nih.gov/pubmed/36922975 http://dx.doi.org/10.3389/fmicb.2023.1123803 |
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