Functional attribution of LdISP, an endogenous serine protease inhibitor from Leishmania donovani in promoting infection.

Leishmaniasis, a parasitic disease caused by unicellular eukaryotic protozoa of the genus Leishmania, affects more than 12 million people worldwide. Events of leishmaniasis are based on the infection of the mammalian host, precisely macrophages, where both host and parasite derived proteases and endogenous inhibitors are significant. Pathogen derived protease inhibitors have generated considerable interest as they often act as an agent promoting infection and parasitic survivability. An endogenous serine protease inhibitor from Indian strain of Leishmania donovani was previously identified by our group and named as LdISP. It has been found to inhibit neutrophil elastase (NE), responsible for natural inflammation process. However, LdISP's role in progression of infection or the proteomics based structural exposition has not been explored. The present study is aimed to localize and validate the potential role of LdISP in infectivity. We found that LdISP localized endogenously and treatment of infected host cells with LdISP curbs ROS and NO production. Additionally, in silico studies are carried out to predict the putative amino acid residues of LdISP involved in the inhibition process. Taken together, our results demonstrate that LdISP eventually exerts a pronounced role in L. donovani infection.