Parveen, S. and Bandhyopadhyay , S. and Das , S. and Bhattacharyya, M.S. and Jawed , J.J. and Paul Chowdhury , B. and Saha, B. and Majumdar , S. (2016) Mycobacterium indicus pranii (Mw)-mediated protection against Visceral Leishmaniasis by reciprocal regulation of host dual specific phosphatases. International Immunology .

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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 competes 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 L. 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-β with DUSP6 increases by Mw treatment resulting into decreased Interlukin-10 (IL-10), phosphorylation of ERK1/2 and Arginase I, whereas, Mw treatment decreases association between Protein Kinase C-ε and DUSP1 resulting into increased Interlukin-12 (IL-12), phosphorylation of p38 and inducible nitric oxide synthase expression. Silencing of DUSP1 or overexpression of DUSP6 in L. donovani infected BALB/c mice decreases parasite burden by inducing IL-12 and reducing IL-10 production. Therefore, we identify DUSP1 and DUSP6 as therapeutic targets, functions of which could be favourably modulated by Mw during L. donovani infection.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	28 Dec 2016 09:29
Last Modified:	28 Dec 2016 09:29
URI:	http://nccs.sciencecentral.in/id/eprint/402

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