Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses

Siegfried Hapfelmeier, Melissa A E Lawson, Emma Slack, Jorum K. Kirundi, Maaike Stoel, Mathias Heikenwalder, Julia Cahenzli, Yuliya Velykoredko, Maria L. Balmer, Kathrin Endt, Markus B. Geuking, Roy Curtiss, Kathy D. McCoy, Andrew J. Macpherson

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Abstract

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 languageEnglish (US)
Pages (from-to)1705-1709
Number of pages5
JournalScience
Volume328
Issue number5986
DOIs
StatePublished - Jun 25 2010

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    Hapfelmeier, S., Lawson, M. A. E., Slack, E., Kirundi, J. K., Stoel, M., Heikenwalder, M., Cahenzli, J., Velykoredko, Y., Balmer, M. L., Endt, K., Geuking, M. B., Curtiss, R., McCoy, K. D., & Macpherson, A. J. (2010). Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science, 328(5986), 1705-1709. https://doi.org/10.1126/science.1188454