Inhibition of groups 1 and 2 CD1 molecules on human dendritic cells by Leishmania species

Dendritic cells are potent immune-activating cells, which traditionally are thought of as presenters of protein antigen to lymphocytes to initiate an immune response. Recently, another mechanism of immune surveillance, the detection of lipid antigens, has been found to be mediated by the nonpolymorphic family of CD1 molecules. There are two different CD1 families, Group 1 consisting of CD1a, CD1b and CD1c, and Group 2 consisting only of CD1d. Leishmania donovani-infected dendritic cells have previously been demonstrated to exhibit decreased surface levels of Group 1 CD1 molecules and are no longer able to initiate a CD1b-restricted T cell response. In contrast to L. donovani, which disseminates to the visceral organs, L. major remains localized, forming a cutaneous lesion. We investigate here whether L. major, the aetiological agent of cutaneous leishmaniasis, also inhibits CD1 expression. We demonstrate that infection of human monocyte-derived dendritic cells with either L. major or L. donovani results in transcriptional down-regulation of both Groups 1 and 2 CD1 molecules. Furthermore, infection of monocytes during differentiation results in a cell phenotype similar to undifferentiated monocytes. Finally, we demonstrate that this down-regulation is not mediated by lipophosphoglycan or other phosphoglycans.