IgA response to symbiotic bacteria as a mediator of gut homeostasis.
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.
Peterson
Daniel A
DA
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA.
McNulty
Nathan P
NP
Guruge
Janaki L
JL
Gordon
Jeffrey I
JI
D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology*; D016667:Bacterial Capsules / Q000276:immunology; D001439:Bacteroides / Q000502:physiology*; D001442:Bacteroides Infections / Q000276:immunology* / Q000382:microbiology*; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D000939:Epitopes / Q000276:immunology; D015870:Gene Expression; D005798:Genes, Bacterial / Q000235:genetics; D016654:Genes, RAG-1; D005856:Germ-Free Life; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis; D007070:Immunoglobulin A / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013559:Symbiosis
D000907:Antibodies, Bacterial; D000939:Epitopes; D018398:Homeodomain Proteins; D007070:Immunoglobulin A; C064658:RAG-1 protein; D052247:Nitric Oxide Synthase Type II