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.
Highlights
The gut microbiota is essential for host physiology, as it regulates the metabolism, epithelial barrier integrity, and immune system development and function (Bäckhed et al, 2005; Artis, 2008; Belkaid and Hand, 2014)
These observations suggest that Immunoglobulin A (IgA)–OVA immune complexes bind to bacterial surfaces even when antibody-binding sites are occupied by their cognate antigen in vivo
We measured antibody binding to cultured B. theta and other members of Bacteroidales and found that 7-6IgA binding was predominant within the metabolically active SybrGreen-positive fraction (Maurice et al, 2013; Fig. 2, A and B). 7-6IgA bound to ethanol-fixed and heat-killed B. theta, which suggests that 7-6IgA may bind to cell wall components generated by bacteria that are present following bacterial death (Fig. 2 C)
Summary
The gut microbiota is essential for host physiology, as it regulates the metabolism, epithelial barrier integrity, and immune system development and function (Bäckhed et al, 2005; Artis, 2008; Belkaid and Hand, 2014). In our previous studies using immunodeficient mouse strains, we found that IgA plays an important role in controlling the composition and geographical distribution of bacterial communities along the gastrointestinal tract (Fagarasan et al, 2002; Suzuki et al, 2004; Kawamoto et al, 2012). This homeostatic role of IgA in regulating commensal bacteria was recently confirmed in humans with IgA deficiency (Fadlallah et al, 2018). With respect to gram-positive species in particular, has been attributed to Fab fragment–independent interactions with the glycans associated with both antibody chains and the secretory component (Mathias and Corthésy, 2011)
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