title: 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.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Shabina
authors.initials: S
authors.lastname: Parveen
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Syamdas
authors.initials: S
authors.lastname: Bandhyopadhyay
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Sonali
authors.initials: S
authors.lastname: Das
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Suchandra Bhattacharyya
authors.initials: SB
authors.lastname: Majumdar
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Junaid Jibran
authors.initials: JJ
authors.lastname: Jawed
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India.
authors.forename: Bidisha Paul
authors.initials: BP
authors.lastname: Chowdhury
authors.affiliation: Department of Pathogenesis & Cellular Response, National Centre for Cell Science, Ganeshkhind, Pune 411 007, Maharashtra, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700 054, West Bengal, India subrata@jcbose.ac.in.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D007155:Immunologic Factors / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology*; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology / Q000378:metabolism*; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D007155:Immunologic Factors; D010744:Phosphoric Monoester Hydrolases
keywords: 
  Leishmania
  ; 
  Mw
  ; dual-specificity phosphatases; visceral leishmaniasis