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Science 325 (5940): 617-620

Copyright © 2009 by the American Association for the Advancement of Science

Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism

Emma Slack,1,5,* Siegfried Hapfelmeier,1,5 Bärbel Stecher,2 Yuliya Velykoredko,1 Maaike Stoel,1 Melissa A. E. Lawson,1 Markus B. Geuking,1 Bruce Beutler,3 Thomas F. Tedder,4 Wolf-Dietrich Hardt,2 Premysl Bercik,1 Elena F. Verdu,1 Kathy D. McCoy,1 Andrew J. Macpherson1,5,*

Abstract: Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body’s cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.

1 Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada.
2 Institute of Microbiology, ETH Zürich, 8032 Zürich, Switzerland.
3 Department of Genetics, The Scripps Research Institute, La Jolla, CA 92121, USA.
4 Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
5 DKF (Department of Clinical Research), Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3008 Bern, Switzerland.

* To whom correspondence should be addressed. E-mail: andrew.macpherson{at} (A.J.M.); emma.slack{at} (E.S.)

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