title: Proteobacteria-specific IgA regulates maturation of the intestinal microbiota.
abstract: The intestinal microbiota changes dynamically from birth to adulthood. In this study we identified γ-Proteobacteria as a dominant phylum present in newborn mice that is suppressed in normal adult microbiota. The transition from a neonatal to a mature microbiota was in part regulated by induction of a γ-Proteobacteria-specific IgA response. Neocolonization experiments in germ-free mice further revealed a dominant Proteobacteria-specific IgA response triggered by the immature microbiota. Finally, a role for B cells in the regulation of microbiota maturation was confirmed in IgA-deficient mice. Mice lacking IgA had persistent intestinal colonization with γ-Proteobacteria that resulted in sustained intestinal inflammation and increased susceptibility to neonatal and adult models of intestinal injury. Collectively, these results identify an IgA-dependent mechanism responsible for the maturation of the intestinal microbiota.
authors.affiliation: Department of Pediatrics; Division of Neonatal-Perinatal Medicine; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Mirpuri
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Raetz
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Sturge
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Wilhelm
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Benson
authors.affiliation: Department of Pediatrics; Division of Neonatal-Perinatal Medicine; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Rashmin C
authors.initials: RC
authors.lastname: Savani
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA; Howard Hughes Medical Institute; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007422:Intestines / Q000254:growth & development* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D020560:Proteobacteria / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A
keywords: IgA; colitis; microbiota; necrotizing enterocolitis; proteobacteria