Clec12a tempers inflammation while restricting expansion of a colitogenic commensal

• Published in: bioRxiv : the preprint server for biology
• Main Authors: 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, Oâ Connell, Ryan M, Zac Stephens, W, Round, June L
• Format: Journal Article
• Language: English
• Published: United States 16.03.2023
• DOI: 10.1101/2023.03.16.532997

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