PURPOSE OF THE STUDY.
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.
The authors developed a strain of mice that did not express the RegIIIγ protein (“RegIIIγ(−/−)” mice). The authors then tested the effects of the gene deletion on the separation between the small-bowel mucosa and luminal bacterial, and also T-cell, inflammation in the intestinal wall.
RegIIIγ, a secreted antibacterial lectin, was found to be essential for maintaining a ∼50-μm zone that physically separates the microbiota from the small-intestinal epithelial surface. Interestingly, colonic mucosa expressed relatively little RegIIIγ, and gene deletion did not affect relationships with bacteria in the colon. Loss of host-bacterial segregation in RegIIIγ(−/−) mice was coupled to increased bacterial colonization of the small-intestinal epithelial surface and enhanced activation of intestinal adaptive immune responses by the microbiota.
The authors conclude that RegIIIγ is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host in the intestine. These findings could be relevant to the pathogenesis of inflammatory bowel disease and other disorders of chronic intestinal inflammation.
Have you ever wondered why the mucosal immune system in the intestines can tolerate the huge amounts of bacteria, along with endotoxin and other immunostimulants packed into the intestines? Even a tiny fraction of this material in the peritoneum or bloodstream would cause sepsis and/or shock. This fascinating article illustrates (literally) a mechanism by which an antibacterial lectin known as RegIIIγ maintains a bacteria-free zone next to the small intestinal epithelium that forms a barrier against bacterial invasion of the epithelium and induction of inflammation. The photomicrographs in the article are striking and clearly visualize the effects of this innate immune mechanism. Interestingly, other studies have shown that this same molecule is also expressed in the airways and has antibacterial functions in the respiratory tract. Understanding the regulation and function of RegIIIγ may lead to new insights into the pathogenesis and treatment of inflammatory and infectious diseases in both anatomic locations.
- Copyright © 2012 by the American Academy of Pediatrics