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The Antibacterial Lectin RegIII Promotes the Spatial Segregation of Microbiota and Host in the Intestine
Shipra Vaishnava,1
Miwako Yamamoto,1
Kari M. Severson,1
Kelly A. Ruhn,1
Xiaofei Yu,1
Omry Koren,3
Ruth Ley,3
Edward K. Wakeland,1
Lora V. Hooper1,2,*
Abstract:
The mammalian intestine is home to ~100 trillion bacteria that perform important metabolic functions for their hosts. The proximity of vast numbers of bacteria to host intestinal tissues raises the question of how symbiotic host-bacterial relationships are maintained without eliciting potentially harmful immune responses. Here, we show that RegIII, a secreted antibacterial lectin, is essential for maintaining a ~50-micrometer zone that physically separates the microbiota from the small intestinal epithelial surface. Loss of host-bacterial segregation in RegIII–/– mice was coupled to increased bacterial colonization of the intestinal epithelial surface and enhanced activation of intestinal adaptive immune responses by the microbiota. Together, our findings reveal that RegIII is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host.
1 Department of Immunology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. 2 The Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. 3 Department of Microbiology, Cornell University, Ithaca, NY 14853, USA.
* To whom correspondence should be addressed. E-mail:lora.hooper{at}utsouthwestern.edu
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