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


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.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:19 Jan 2011 17:41
Last Modified:05 Apr 2016 14:36
Publisher:American Association for the Advancement of Science (AAAS)
ISSN:0036-8075
Additional Information:Comment in: Science. 2010 Jun 25;328(5986):1646-7.
Publisher DOI:10.1126/science.1188454
PubMed ID:20576892
Permanent URL: http://doi.org/10.5167/uzh-42633

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