Title | Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Zeng MY, Cisalpino D, Varadarajan S, Hellman J, H Warren S, Cascalho M, Inohara N, Nunez G |
Journal | Immunity |
Volume | 44 |
Issue | 3 |
Pagination | 647-658 |
Date Published | 2016 Mar 15 |
ISSN | 1097-4180 |
Keywords | Animals, Bacterial Load, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Homeostasis, Host-Pathogen Interactions, Immunoglobulin G, Intestines, Mice, Mice, Inbred C57BL, Mice, Knockout, Microbiota, Peptidoglycan, Toll-Like Receptor 2, Toll-Like Receptor 4 |
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. |
DOI | 10.1016/j.immuni.2016.02.006 |
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Alternate Journal | Immunity |
PubMed ID | 26944199 |
PubMed Central ID | PMC4794373 |
Grant List | DK095782 / DK / NIDDK NIH HHS / United States R01 DK091191 / DK / NIDDK NIH HHS / United States T32DK094775 / DK / NIDDK NIH HHS / United States T32 HL007517 / HL / NHLBI NIH HHS / United States R01 GM59694 / GM / NIGMS NIH HHS / United States NIH 5P30DK034933 / DK / NIDDK NIH HHS / United States R01 GM059694 / GM / NIGMS NIH HHS / United States DK091191 / DK / NIDDK NIH HHS / United States R21 AI117561 / AI / NIAID NIH HHS / United States T32HL007517 / HL / NHLBI NIH HHS / United States P30 DK034933 / DK / NIDDK NIH HHS / United States 5R21AI117561 / AI / NIAID NIH HHS / United States R01 DK095782 / DK / NIDDK NIH HHS / United States T32 DK094775 / DK / NIDDK NIH HHS / United States |