Study of the role of CCR5 in a mouse model of intranasal challenge with Yersinia pestis

CCR5 is a chemokine receptor used by HIV-1 to enter cells and has recently been found to act as a pathogen associated molecule pattern receptor. Current positive selection for the high frequency of a CCR5-Delta32 allele in humans has been attributed to resistance to HIV, smallpox, and plague infections. Using an intranasal mouse model of Y. pestis infection, we have found that lack of CCR5 does not enhance host resistance to Y. pestis infection and that CCR5-mediated responses might have a protective role. CCR5-/- mice exhibited higher levels of circulating RANTES and MIP-1alpha than those exhibited by wild-type mice at the baseline and throughout the course of Y. pestis infection. High levels of RANTES and MIP-1alpha, which are CCR5 ligands that mediate Natural Killer cell migration, may reflect compensation for the absence of CCR5 signaling.