IgA response to symbiotic bacteria as a mediator of gut homeostasis.

By D. Peterson, N. McNulty, J. Guruge, Jeffrey I. Gordon. Cell Host and Microbe, 2007

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Colonization of germ-free mice with a normal gut microbiota elicits bacteria-specific IgA antibody responses. The effects of these responses on microbial and host biology remain poorly defined. Therefore, we developed a gnotobiotic mouse model where the microbiota is reduced to one bacterial species, and the antibody repertoire to a single, monoclonal IgA against the bacterium's capsular polysaccharide. Bacteroides thetaiotaomicron was introduced into germ-free wild-type, immunodeficient Rag1(-/-), or Rag1(-/-) mice harboring IgA-producing hybridoma cells. Without IgA, B. thetaiotaomicron elicits a more robust innate immune response and reacts to this response by inducing genes that metabolize host oxidative products. IgA reduces intestinal proinflammatory signaling and bacterial epitope expression, thereby balancing suppression of the oxidative burst with the antibody's negative impact on bacterial fitness. These results underscore the adaptive immune system's critical role in establishing a sustainable host-microbial relationship. Immunoselection of bacterial epitope expression may contribute to the remarkable strain-level diversity in this ecosystem.

Subfields: Immunology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5b7488f46dcf1cf5a2fbc064bb9bb470bf131f41

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Citations in the corpus

The regulation of IgA class switching (2008, background): “Furthermore, sIgA promotes the establishment of a mutualistic host–microbe relationship by downmodulating the expression of pro-inflammatory epitopes by commensal bacteri”
Role of the Microbiota in Immunity and inflammation (2014, background): “, 2009) thereby controlling the host relationship with the microbiota via multiple mechanisms (Peterson et al., 2007; Suzuki et al., 2004) (Figure 2).”
The immune system and the gut microbiota: friends or foes? (2010, background): “and secretory IgA, which in turn contain the microbiota within the intestinal lumen and neutralize MAMP”
Identifying genetic determinants needed to establish a human gut symbiont in its habitat (2009, neutral): “thetaiotaomicron have identified a few fitness determinants that could serve as reference controls for the present study (Peterson et al., 2007).”
Worlds within worlds: evolution of the vertebrate gut microbiota (2008, background): “The adaptive immune system mediates tolerance to the gut microbiota through immunoglobulin A (IgA) production in a way that suggests the need for perpetual modification of surface microbial epitope”
The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. (2009, background): “, 2002) and bacterial translocation (Macpherson and Uhr, 2004) and by minimizing flora-induced activation of the host oxidative system (Peterson et al., 2007).”
The Microbiome in Infectious Disease and Inflammation (2012, neutral): “thetaiotaomicron is otherwise commensal to the host, but in the absence of IgA it elicits a robust innate immune response, including the induction of iNOS, and then adapts by inducing bacterial genes involved in nitric oxide metabolism (25).”
Defining dysbiosis and its influence on host immunity and disease (2014, background): “, 2007), production of antibodies that can directly bind to and influence microbial function (Fagarasan and Honjo, 2003; Peterson et al., 2007; Slack et al., 2012) and anti-inflammatory T cells.”