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Mycobacterium indicus pranii (Mw)-mediated protection against visceral leishmaniasis by reciprocal regulation of host dual-specificity phosphatases.

Abstract

Leishmania donovani resides within the host macrophages by dampening host defence mechanisms and thereby it modulates the host cell functions for its survival. Multiple host cell factors compete during the interplay between the host and the parasite. Roles for dual-specificity 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 the TLR4 pathway. Association of PKC-β with DUSP6 increases after Mw treatment resulting in decreased IL-10, phosphorylation of ERK1/2 and Arginase-1, whereas Mw treatment decreases the association between PKC-ε and DUSP1 resulting in increased IL-12, phosphorylation of p38 and inducible nitric oxide synthase expression. Silencing of DUSP1 or over-expression of DUSP6 in L. donovani-infected BALB/c mice decreases the 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.

More information

Type
Journal Article
Author
Parveen S
Bandhyopadhyay S
Das S
Majumdar SB
Jawed JJ
Chowdhury BP
Saha B
Majumdar S
Year of Publication
2016
Journal
International immunology
Volume
28
Issue
12
Number of Pages
585-595
Language
eng
ISSN Number
1460-2377
DOI
10.1093/intimm/dxw049
Alternate Journal
Int. Immunol.
Publication Language
eng