DOI: 10.1101/2023.03.16.532997

Clec12a tempers inflammation while restricting expansion of a colitogenic commensal

J.Round T. Chiaro K. Bauer K. Ost E. Stephen-Victor M. Nelson J. H. Hill R. Bell M. Harwood W. Voth T. Jackson K. Klag R. O'Connell W. Z. Stephens

J.Round T. Chiaro K. Bauer ...+10 W. Z. Stephens

摘要

Regulation 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 with F. rodentium was 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 uptake F. rodentium. Purified Clec12a had higher binding to gram-positive organisms such as F. rodentium. Thus, our data identifies Clec12a as an innate immune surveillance mechanism to control expansion of potentially harmful commensals without overt inflammation.

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