Leishmania donovani mevalonate kinase regulates host actin for inducing phagocytosis

Abstract

Despite the well-established role of macrophages in phagocytosing Leishmania, the contribution of the parasite to this process is not well understood. Present study provides insights into the mechanism underlying the MVK-induced entry of L. donovani and improve our knowledge of host-pathogen interactions. We have discussed Mevalonate kinase (MVK)-induced actin reorganization, modulation of signaling pathways and host cell functions. Our results show that LdMVK gains access to macrophage cytosol and induces actin assembly modulation through the activation of actin-related proteins: VASP, Src and ERM. We have also demonstrated that LdMVK induces Ca2+ signaling and Akt pathway in macrophages, which are critical components of Leishmania survival and proliferation. Interestingly, we found that antibodies against LdMVK can kill Leishmania-infected macrophages in culture by forming extracellular traps, highlighting the potential of LdMVK in inhibiting parasite death. Overall, LdMVK is a virulent factor in Leishmania that mediates parasite internalization and host modulation by targeting host proteins phosphorylation and calcium homeostasis having significant implications in disease progression.