Commensal Gram-positive Bacteria Initiates Colitis by Inducing Monocyte/Macrophage Mobilization

Y Nakanishi, T Sato and T Ohteki.

Mucosal Immunology (2015) 8, 152–160; doi:10.1038/mi.2014.53; published online 18 June 2014

Back to Front: Yusuke Nakanishi and Toshiaki Ohteki

Back to Front: Yusuke Nakanishi and Toshiaki Ohteki

The commensal bacteria in the intestine benefit the host immune response. However, breakdown of the intestinal epithelial layer’s barrier function results in the inflow of commensal flora and improper immune responses against the commensal flora, leading to inflammatory bowel disease (IBD) development. The early stages of IBD commonly induce the recruitment of innate immune cells, including monocytes and macrophages, to the colon. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, we showed that the monocytes/macrophages infiltrating the colon are an exclusive population producing TNF-, a representative colitogenic cytokine. Notably, pretreating mice with vancomycin, which eliminated Gram-positive bacteria, particularly the Lachnospiraceae family, significantly reduced the severity of the colitis by selectively blocking the recruitment of monocytes/macrophages, but not of other cells. Vancomycin treatment specifically downregulated the colonic epithelial cell (cEC) expression of CCR2 ligands, which are critical chemokines for monocyte/macrophage mobilization into the inflamed colon. As the sera from Crohn’s disease patients and colitic mice react with Lachnospiraceae bacterium A4 flagella, our findings provide a new environmental risk factor and new therapeutic approaches for IBD. Click Here to Read the Article.