Back to Search
Start Over
Clec12a tempers inflammation while restricting expansion of a colitogenic commensal.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 16. Date of Electronic Publication: 2023 Mar 16. - Publication Year :
- 2023
-
Abstract
- 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 <superscript>-/-</superscript> 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 <superscript>-/-</superscript> macrophages revealed heighten inflammation but marked reduction in genes associated with phagocytosis. Indeed, Clec12a <superscript>-/-</superscript> 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.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 36993296
- Full Text :
- https://doi.org/10.1101/2023.03.16.532997