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The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.

Original publication

DOI

10.1126/science.1188454

Type

Journal article

Journal

Science

Publication Date

25/06/2010

Volume

328

Pages

1705 - 1709

Keywords

Animals, Antibodies, Bacterial, Antibody Specificity, Colony Count, Microbial, Dose-Response Relationship, Immunologic, Escherichia coli, Germ-Free Life, Half-Life, Immunoglobulin A, Immunologic Memory, Intestinal Mucosa, Intestines, Mice, Mice, Inbred C57BL, Mucous Membrane, Plasma Cells, Time Factors