Studies in several models of
inflammation have underscored the importance of P- and E-
selectins in the migration of T cells to inflamed tissues. However, the role of the endothelial
selectins in
infection-induced cutaneous
inflammation and host-protective immunity has not been investigated. In this study, we demonstrate that CD4(+) T cells recruited to the cutaneous compartment during
infection with Leishmania major express P- and
E-selectin ligands. Furthermore, expression of P- and
E-selectin ligands correlates with activated Leishmania-specific Th1 cells and is dependent upon
IL-12. To investigate the functional role of the endothelial
selectins during
leishmaniasis, we infected mice either singly or doubly deficient in the expression of P- and E-
selectins. Mice lacking both P- and E-
selectins developed significantly less
inflammation at the site of a primary and
secondary infection, and exhibited an impaired delayed-type
hypersensitivity response. Surprisingly, the absence of the endothelial
selectins had no effect on the control of parasite replication or immunity to
reinfection. Thus, these data demonstrate that although the endothelial
selectins contribute to the inflammatory response, they are not required for protective immunity to L. major. Moreover, these data suggest that by blocking P- and E-
selectins, the immune pathology associated with
cutaneous leishmaniasis might be ameliorated without compromising immunity to
infection.