Regulation of PKC Mediated Signaling by Calcium during Visceral Leishmaniasis

Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca(2+) pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca(2+) homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca(2+) concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca(2+)-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca(2+). Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca(2+) in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca(2+)-ATPases play prominent roles during visceral leishmaniasis.