Author:
Chiaro Tyson R.,Bauer Kaylyn M.,Ost Kyla S.,Stephen-Victor Emmanuel,Nelson Morgan C.,Hill Jennifer H.,Bell Rickesha,Harwood Morgan,Voth Warren,Jackson Taylor,Klag Kendra A,O’Connell Ryan M.,Zac Stephens W.,Round June L.
Abstract
SUMMARYRegulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a-/-mice that was marked by expansion of the gram-positive organism,Faecalibaculum rodentium. Treatment withF. rodentiumwas sufficient to worsen colitis in wild-type mice. Macrophages within the gut express the highest levels of Clec12a. Cytokine and sequencing analysis in Clec12a-/-macrophages revealed heighten inflammation but marked reduction in genes associated with phagocytosis. Indeed, Clec12a-/-macrophages are impaired in their ability to uptakeF. rodentium.Purified Clec12a had higher binding to gram-positive organisms such asF. rodentium. Thus, our data identifies Clec12a as an innate immune surveillance mechanism to control expansion of potentially harmful commensals without overt inflammation.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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