title: Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens.
abstract: The gut microbiota is compartmentalized in the intestinal lumen and induces local immune responses, but it remains unknown whether the gut microbiota can induce systemic response and contribute to systemic immunity. We report that selective gut symbiotic gram-negative bacteria were able to disseminate systemically to induce immunoglobulin G (IgG) response, which primarily targeted gram-negative bacterial antigens and conferred protection against systemic infections by E. coli and Salmonella by directly coating bacteria to promote killing by phagocytes. T cells and Toll-like receptor 4 on B cells were important in the generation of microbiota-specific IgG. We identified murein lipoprotein (MLP), a highly conserved gram-negative outer membrane protein, as a major antigen that induced systemic IgG homeostatically in both mice and humans. Administration of anti-MLP IgG conferred crucial protection against systemic Salmonella infection. Thus, our findings reveal an important function for the gut microbiota in combating systemic infection through the induction of protective IgG.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Melody Y
authors.initials: MY
authors.lastname: Zeng
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisalpino
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Saranyaraajan
authors.initials: S
authors.lastname: Varadarajan
authors.affiliation: Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Hellman
authors.affiliation: Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.affiliation: Transplantation Biology, Department of Surgery and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Marilia
authors.initials: M
authors.lastname: Cascalho
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: gabriel.nunez@umich.edu.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics; D054884:Host-Pathogen Interactions; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D010457:Peptidoglycan / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D007074:Immunoglobulin G; D010457:Peptidoglycan; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4