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,*
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.
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}insel.ch (A.J.M.); emma.slack{at}dkf.unibe.ch (E.S.)
