Journal
SCIENCE
Volume 328, Issue 5986, Pages 1705-1709Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1188454
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Funding
- Swiss National Science Foundation [310030_124732]
- Canadian Institutes of Health Research
- Crohn's and Colitis Foundation of Canada
- Genome Canada
- Farncombe Foundation
- Canadian Association of Gastroenterology
- Canada Research Chairs program
- Oncosuisse Foundation [OCS 02113-08-2007]
- German Science Foundation
- Swiss National Science Foundation (SNF) [310030_124732] Funding Source: Swiss National Science Foundation (SNF)
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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.
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