IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria

Author:

Nakajima Akira1,Vogelzang Alexis2,Maruya Mikako2,Miyajima Michio2,Murata Megumi1,Son Aoi1,Kuwahara Tomomi3,Tsuruyama Tatsuaki4,Yamada Satoshi5,Matsuura Minoru5ORCID,Nakase Hiroshi56,Peterson Daniel A.7,Fagarasan Sidonia2,Suzuki Keiichiro12ORCID

Affiliation:

1. Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

2. Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan

3. Department of Microbiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

4. Center for Anatomical, Pathological, Forensic Medical Research and Department of Drug and Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

5. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

6. Department of Gastroenterology and Hepatology, School of Medicine, Sapporo Medical University, Sapporo, Japan

7. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD

Abstract

Immunoglobulin A (IgA) promotes health by regulating the composition and function of gut microbiota, but the molecular requirements for such homeostatic IgA function remain unknown. We found that a heavily glycosylated monoclonal IgA recognizing ovalbumin coats Bacteroides thetaiotaomicron (B. theta), a prominent gut symbiont of the phylum Bacteroidetes. In vivo, IgA alters the expression of polysaccharide utilization loci (PUL), including a functionally uncharacterized molecular family provisionally named Mucus-Associated Functional Factor (MAFF). In both mice and humans, MAFF is detected predominantly in mucus-resident bacteria, and its expression requires the presence of complex microbiota. Expression of the MAFF system facilitates symbiosis with other members of the phylum Firmicutes and promotes protection from a chemically induced model of colitis. Our data reveal a novel mechanism by which IgA promotes symbiosis and colonic homeostasis.

Funder

Japanese government

Astellas Pharma Inc.

Japanese Ministry of Education, Culture, Sports, Science, and Technology

Mochida Memorial Foundation for Medical and Pharmaceutical Research

Ministry of Health, Labor, and Welfare of Japan

RIKEN

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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