Stressor-enhanced colitis is abrogated in mice deficient in CCL2 (61.6)

Abstract

Abstract Exposing mice to a social stressor called social disruption (SDR) has been reported to increase CD11b+Ly-6ChiCCR2+ inflammatory monocytes in the circulation and spleen. This study was designed to test the hypothesis that stressor-induced exacerbation of pathogen-induced colitis is dependent upon CCL2-mediated recruitment of inflammatory monocytes. Mice deficient in CCL2 (i.e., CCL2-/-), a chemokine involved in the recruitment of CCR2+ monocytes, and wild type C57BL/6 mice were challenged with the colonic pathogen Citrobacter rodentium during exposure to SDR. Exposing mice to SDR, which consists of intermale aggression for 2 hrs a night on 6 consecutive nights, during challenge with C.rodentium significantly increased pathogen-induced colitis. This increase was marked by an enhanced accumulation of F4/80+ colonic monocytes/macrophages, increased pathogen burden and pathogen-induced colonic histopathology, and increased inflammatory cytokine and chemokine gene expression in comparison to C. rodentium-challenged non-stressed control. These stressor effects were dependent upon CCL2, since exposing CCL2-/- mice to SDR did not lead to an increased accumulation of colonic monocytes/macrophages in the colon and did not significantly increase gene expression or pathogen-induced histopathology. Together, these data illustrate the deleterious effects of stressor-enhanced recruitment of inflammatory monocytes during bacterial challenge.