Reversible Microbial Colonization of Germ-Free Mice Reveals the Dynamics of IgA Immune Responses
2010
Hapfelmeier, Siegfried | Lawson, Melissa A.E. | Slack, Emma | Kirundi, Jorum K. | Stoel, Maaike | Heikenwalder, Mathias | Cahenzli, Julia | Velykoredko, Yuliya | Balmer, Maria L. | Endt, Kathrin | Geuking, Markus B. | Curtiss, Roy 3rd | McCoy, Kathy D. | Macpherson, Andrew J.
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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