Leishmania major lipophosphoglycan modulates the phenotype and inhibits migration of murine Langerhans cells.

Abstract

Langerhans cells (LC), members of the dendritic cell family, play a central role in the initiation and regulation of the immune response against the protozoan parasite Leishmania major. LC take up antigens in the skin and transport them to the regional lymph nodes for presentation to T cells. However, it is not known whether LC functions are modulated by parasite antigens. In the present study, we examined the effect of a major parasite surface molecule, L. major lipophosphoglycan (LPG), on the maturation of LC and their migratory properties. The results show that exposure to LPG did not affect the expression of MHC class II and B7, but induced an up-regulation of CD25, CD31 and VE-cadherin expression and a down-regulation of Mac-1 expression by LC. Importantly, LPG treatment inhibited the migratory activity of LC, as it reduced their efflux from skin explants and their migration in transwell cultures. These results suggest that Leishmania LPG impairs LC migration out of the skin and, thus, may modulate their immunostimulatory functions, which require LC translocation from skin to lymph nodes.