RESUMEN
PURPOSE: Leishmania transmission by sand flies is detected by dermal cells that recognize ligands, such as lipophosphoglycan (LPG) on the promastigote glycocalyx. Resident dermal cells include γδ T cells, that recognize antigens by TCR or innate receptors, such as TLRs. We analyzed the response of dermal γδ T cells to Leishmania mexicana infections or inoculation of LPG, and whether parasite LPG activates γδ T cells through TLR2. METHODS: We stimulated γδ T cells with LPG and analyzed colocalization of LPG and TLR2 by confocal microscopy. Activation of TLR2 was evaluated by IκBα phosphorylation. BALB/c mice were inoculated with L. mexicana or LPG in the dermis of earlobes, and LPG+ TLR2+ γδ T cells were analyzed by flow cytometry. TNF+ γδ T cells were examined in earlobe dermis by confocal microscopy. RESULTS: Stimulation with purified LPG showed activation of TLR2 with IκBα phosphorylation in γδ T cells. Inoculation of L. mexicana parasites or LPG into earlobe dermis showed co-expression of LPG+ and TLR2+ in γδ T cells, demonstrating their interaction during infections. A subset of γδ T cells (LPG+ and TLR2-) provided evidence that additional receptors recognize LPG. Inoculation of LPG enhanced overall γδ T cell numbers, including those expressing TNF, whereas infection with the parasite mostly enhanced γδ T cells expressing TNF. CONCLUSION: L. mexicana LPG is a ligand recognized by TLR2 on γδ-T cells leading to their activation, although contribution of other receptors cannot be ruled out and need to be analyzed to elucidate their contribution during Leishmania infections.