Adhikari, , A and Majumder, , S and Banerjee, , S and Gupta, , G and Bhattacharya, P. and Bhattacharya, S. and Majumder, , and Saha , B. and Majumder, , S. (2012) Mycobacterium indicus pranii (Mw)-mediated protection against visceral leishmaniasis: involvement of TLR4 signalling. J Antimicrob Chemother , 2 (67). pp. 2892-2902.

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Abstract

Objectives: The aim of this study was to characterize the antileishmanial activity of heat-killed Mycobacterium indicus pranii (Mw) alone or in combination with a subtoxic dose of amphotericin B [AMB(st)]. Methods: Mw- and Mw+AMB(st)-mediated antileishmanial activity was evaluated by microscopic counting of intracellular amastigotes in Giemsa-stained macrophages and real-time PCR analysis of inducible nitric oxide synthase (iNOS) expression and measurement of nitric oxide generation by Griess reagent. The relationship between Mw and Toll-like receptor 4 (TLR4) signalling was studied by fluorescence-activated cell sorting, western blot and confocal microscopy. The effect of Mw alone or in combination with AMB(st) on the expression and production of interleukin (IL)-12, tumour necrosis factor-a, IL-10 and transforming growth factor-b was analysed by real-time PCR and ELISA, respectively. Results: Mw treatment alone or with AMB(st) caused a significant increase in TLR4 expression of L. donovaniinfected macrophages along with the activation of TLR4 downstream signalling, facilitating active nuclear translocation of nuclear factor kB (NF-kB). These events culminated in the up-regulation of the proinflammatory response, which was abrogated by treatment with TLR4-specific small-interfering RNA. In addition, this study demonstrates that this chemoimmunotherapeutic strategy confers protection against leishmanial pathogenesis via TLR4-dependent counter-regulation of inducible nitric oxide synthase (iNOS) and arginase1 activity. Conclusions: These results provide a mechanistic understanding of Mw- or Mw+AMB(st)-mediated protection against leishmanial parasites within host macrophages.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	09 Apr 2015 09:35
Last Modified:	02 Jul 2015 09:39
URI:	http://nccs.sciencecentral.in/id/eprint/25

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