The involvement of TLR2 in cytokine and reactive oxygen species (ROS) production by PBMCs in response to Leishmania major phosphoglycans (PGs)

In the present study, we show for the first time that lipophosphoglycan (LPG) stimulated cytokine production by human peripheral blood mononuclear cells is also mediated via Toll-like receptor (TLR2). In addition, ill order to verify if TLR2 is involved in recognition of the purified PGs, neutralizing mAbs against TLR2 and TLR4 were used to treat the cells before being stimulated with PGs. We found strong Th1-promoting cytokines induced by sLPG but not by mLPG which was blocked by presence of anti-TLR2 mAb. This finding reveals a mechanism by which the first encounter and recognition of L. major promastigotes by mLPG after interaction with TLR2 provides a cytokine milieu for consequent Th2 differentiation. Moreover, having shown the strong induction of Th1-promoting cytokines and low production Of IL-10 in response to sLPG might have vaccine implication since it is recognized by TLR2 providing signals to professional antigen presenting cells that reside in the skin to promote effective T cell responses against Leishmania infection. In addition, it was shown that purified mLPG and sLPG activate reactive oxygen species (ROS) production which is also blocked by anti-TLR2 but not by anti-TLR4. However, no inhibition was seen in PPG-induced cytokine and ROS production in the presence of anti-TLR2 and anti-TLR4, implying involvement of other receptors.