Subrata Majumdar
Bose Institute, India
Title: Regulation of dual specificity phosphatases during Leishmania donovani infection: Critical role of immunomodulators
Biography
Biography: Subrata Majumdar
Abstract
Leishmania donovani resides within the host macrophages by dampening host defense mechanisms and thereby it modulates the host cell functions for its survival. Multiple host cell factors determine who wins the race during the interplay between the host and the parasite. Role of dual specific phosphatases (DUSPs) are implicated in various pathological conditions. However, the reciprocity of these DUSPs was unknown in Leishmania donovani infection in a susceptible model. Here, we show that Mycobacterium indicus pranii (Mw), an immunomodulator, reciprocally regulates DUSP1 and DUSP6 through Toll-like Receptor 4 pathway. Association of Protein Kinase C-b with DUSP6 increases by Mw treatment resulting into decreased Interlukin-10, phosphorylation of ERK1/2 and Arginase I, whereas, Mw treatment decreases association between Protein Kinase C-e and DUSP1 resulting into increased Interlukin-12, phosphorylation of p38 and inducible nitric oxide synthase expression. In another study, we found that Leishmania donovani significantly reduced the expression of DUSP4. Glycyrrhizic Acid (GA), an immunomodulator, already known to suppress Leishmania donovani infection, found to up-regulate DUSP4 expression during Leishmania donovani infection. On the other hand, GA fails to increase Th1 cytokine production and decrease Th2 response during DUSP4 knock-down condition suggesting the key role of DUSP4 while giving protection during Leishmania donovani infection. Therefore, we establish that DUSP6, DUSP1 and DUSP4 can be promising therapeutic targets to provide better treatment support to the patients suffering from visceral Leishmaniasis.