Difference in strain pathogenicity of a septicemic Yersinia pestis infection in a TLR2-/- mouse model.

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