@article{29408,
  keywords = {Amphotericin B, Animals, Antiprotozoal Agents, Blotting, Western, Cytokines, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gene Expression Profiling, Humans, Leishmaniasis, Visceral, Macrophages, Mice, Mice, Inbred BALB C, Microscopy, Microscopy, Confocal, Mycobacterium, Nitric Oxide, Nitric Oxide Synthase Type II, Parasite Load, Real-Time Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptor 4},
  author = {Adhikari A and Majumder S and Banerjee S and Gupta G and Bhattacharya P and Majumdar SB and Saha B and Majumdar S},
  title = {Mycobacterium indicus pranii (Mw)-mediated protection against visceral leishmaniasis: involvement of TLR4 signalling.},
  abstract = {<p><strong>OBJECTIVES: </strong>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)].</p>

<p><strong>METHODS: </strong>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-α, IL-10 and transforming growth factor-β was analysed by real-time PCR and ELISA, respectively.</p>

<p><strong>RESULTS: </strong>Mw treatment alone or with AMB(st) caused a significant increase in TLR4 expression of L. donovani-infected macrophages along with the activation of TLR4 downstream signalling, facilitating active nuclear translocation of nuclear factor κB (NF-κB). 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.</p>

<p><strong>CONCLUSIONS: </strong>These results provide a mechanistic understanding of Mw- or Mw + AMB(st)-mediated protection against leishmanial parasites within host macrophages.</p>
},
  year = {2012},
  journal = {The Journal of antimicrobial chemotherapy},
  volume = {67},
  pages = {2892-902},
  issn = {1460-2091},
  doi = {10.1093/jac/dks315},
  language = {eng},
}