Mast cells’ interaction with Leishmania leads to effector responses in reducing initial parasite load

Abstract

Abstract Mast cells (MCs) are involved in clearing invading pathogens at the skin surface and play an important role in innate and adaptive defenses. Hence they may have an important role in the control of Leishmaniasis due to the protozoa Leishmania that are inoculated by infected sandfly vector on the skin surface. It is still unclear if their contributions occur directly through active pathogen killing or antigen uptake. Our objectives were to use Leishmania donovoni the causative agent of fatal visceral Leishmaniasis and L. tropica the causative agent of cutaneous leishmaniasis for studying the interactions between the parasite and MCs to clarify if MCs are directly involved in active antigen uptake, and its clearance. We found that co-culture of Leishmania with MCs led to significant killing of L. tropica and to a lesser extent of L. donovoni. Also, while there was significant uptake of L. tropica by MCs, L. donovoni was not phagocytosed by MCs. Uptake increased with time of exposure in case of L. tropica. We also found significant generation of reactive oxygen species by MCs on co-culture with these species of Leishmania, which may contribute to their clearance. However interactions of MCs with Leishmania led to generation of MC extracellular traps comprising of DNA, histones and tryptase probably to ensnare these pathogens. These results clearly establish that MCs may contribute to host defences to Leishmania in a differential manner by actively taking up these pathogens and also by mounting effector responses for their direct clearance by extracellular and non-phagocytic means. This gives us an understanding that MCs can also be used as a target for therapeutic approaches to leishmaniasis.