A novel role of macrophage PIST protein in regulatingLeishmania majorinfection

Abstract

AbstractPDZ protein interacting specifically with Tc10 or PIST is a mammaliantrans-Golgi resident protein that regulates subcellular sorting of plasma membrane receptors. PIST has recently been found to play an important role in regulating viral pathogenesis. Alteration in PIST expression is linked to the reprogramming of cell surface receptors which is crucial in determining herpes simplex virus1 infection. In this context, PIST is crucial in triggering autophagy via Beclin 1 -PI3KC3 pathway. However, there is complete lack in our knowledge on the role of this protein in any parasitic infection.Leishmaniaparasites infect their host macrophage cells via phagocytosis and their survival within the parasitophorous compartment has recently been found to be dependent on host autophagy by a yet to be identified mechanism. UsingLeishmania major(L. major)-macrophage infection model system we, for the first-time report here that in infected macrophages Golgi resident PIST protein migrates towards the parasite containing compartment. We have also found that PIST associates with Beclin 1, however, not with LC3 withinL. majorparasite containing compartment of infected macrophages. Further, we performed genetic ablation of PIST by siRNA and observed that knockdown of macrophage PIST in turn helps in parasite replication. Contrary to this, overexpression of PIST in macrophages restricted the multiplication ofL. major. Collectively, our study for the first time reveals that PIST is essential in regulating intracellular parasite,L. majorinfection within macrophage cells.Summary StatementMammalian PIST protein plays a crucial role in regulating cellular trafficking events. Here, we showed that PIST status is altered withinLeishmania majorparasite infected macrophages. Further, we confirmed that PIST is essential in restricting parasite growth. Additionally, a potential interacting axis between PIST and Beclin 1 is identified during infection.