Resistance to Yersinia pestis infection decreases rapidly and substantially with age in B10.T(6R) mice (162.9)

Abstract

Abstract We have previously demonstrated that 2-3 month old, female B10.T(6R) mice are highly resistant to a delta pgm strain of Yersinia pestis and by 5 months of age these mice are highly susceptible to Y. pestis infection. In the current study we further characterize this observation in female B10.T(6R) mice. The LD50 of Y. pestis was ~14000 CFU/ml in young (2-3 month) mice while only ~60 CFU/ml in middle aged (>5 month) mice. Significantly elevated bacterial burden was found in both the spleen and liver of middle aged mice while a significant infiltration of immune cells was observed in resistant young mice. The cellular infiltrate in susceptible middle aged was comparable to susceptible young C57BL6/J mice. Sera and spleens from Y. pestis-infected middle aged B10.T(6R) contained elevated levels of KC, MCP-1 (CCL2), MIP-1a (CCL3), G-CSF, IL-6 and Eotaxin. In many cases, cytokine/chemokine levels in middle aged mice increased in an infectious dose-dependent manner and were comparable to Y. pestis infection in C57BL6/J mice with both experimental groups being significantly increased when compared to infected young B10.T(6R) mice with the exception of IL1b that was only increased in both serum and spleen samples from young mice. These findings suggest that IL1b may be critical to prevent Y. pestis infection and may provide insight into defense mechanism(s) necessary to develop resistance to the plague.