Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2 -/- Mouse Model

is the causative agent of bubonic, pneumonic, and septicemic plague. We demonstrate that Toll-like receptor 2-deficient (TLR2 ) mice are resistant to septicemic infection by the KIM5 strain of but not to infection by the CO92 strain. This resistance is dependent on TLR2, the route of infection, and the isoform of YopJ. Elevated bacterial burdens were found in the spleens of CO92 -infected animals by 24 h postinfection and in the livers by 4 days. The YopJ isoform present contributed directly to cytotoxicity and inflammatory cytokine production of bone marrow-derived macrophages from TLR2 mice. Immune cell trafficking is altered in CO92 infections, with an increased neutrophil infiltration to the spleen 5 days postinfection. Immune cell infiltration to the liver was greater and earlier in KIM5-infected TLR2 mice. The functionality of the immune cells was assessed by the ability to develop reactive oxygen and nitrogen species. Our data suggest an inhibition of granulocytes in forming these species in CO92 -infected TLR2 mice. These findings suggest that resistance to KIM5 in TLR2 mice is dependent on early immune cell trafficking and functionality.