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Science 328 (5986): 1705-1709

Copyright © 2010 by the American Association for the Advancement of Science

Reversible Microbial Colonization of Germ-Free Mice Reveals the Dynamics of IgA Immune Responses

Siegfried Hapfelmeier,1,2,* Melissa A. E. Lawson,2 Emma Slack,1,2 Jorum K. Kirundi,1,2 Maaike Stoel,2 Mathias Heikenwalder,3 Julia Cahenzli,2 Yuliya Velykoredko,2 Maria L. Balmer,1 Kathrin Endt,4 Markus B. Geuking,2 Roy Curtiss, 3rd,5 Kathy D. McCoy,2 Andrew J. Macpherson1,2,*

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.

1 DKF (Maurice Müller Laboratories), MEM, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3013 Bern, Switzerland.
2 Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8N 3Z5, Canada.
3 Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
4 Institute of Microbiology, Federal Institute of Technology, 8093 Zurich, Switzerland.
5 Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.

* To whom correspondence should be addressed. E-mail: andrew.macpherson{at}insel.ch (A.J.M.); hapfelmeier{at}gmail.com (S.H.)

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