@article{29413,
  keywords = {Amphotericin B, Animals, Antiprotozoal Agents, Cells, Cultured, Cytokines, Immunotherapy, Interleukin-12, Leishmania donovani, Leishmaniasis, Visceral, Liver, MAP Kinase Signaling System, Macrophage Activation, Macrophages, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Nitric Oxide, Nontuberculous Mycobacteria, Reactive Oxygen Species, Spleen, Th1 Cells},
  author = {Adhikari A and Gupta G and Majumder S and Banerjee S and Bhattacharjee S and Bhattacharya P and Kumari S and Haldar S and Majumdar SB and Saha B and Majumdar S},
  title = {Mycobacterium indicus pranii (Mw) re-establishes host protective immune response in Leishmania donovani infected macrophages: critical role of IL-12.},
  abstract = {<p>Leishmania donovani, a protozoan parasite, causes a strong immunosuppression in a susceptible host and inflicts the fatal disease visceral leishmaniasis. Relatively high toxicity, low therapeutic index, and failure in reinstating host-protective anti-leishmanial immune responses have made anti-leishmanial drugs patient non-compliant and an immuno-modulatory treatment a necessity. Therefore, we have tested the anti-leishmanial efficacy of a combination of a novel immunomodulator, Mycobacterium indicus pranii (Mw), and an anti-leishmanial drug, Amphotericin B (AmpB). We observe that Mw alone or with a suboptimal dose of AmpB offers significant protection against L. donovani infection by activating the macrophages. Our experiments examining the anti-leishmanial activity of Mw alone or with AmpB also indicate a p38MAPK and ERK-1/2 regulated pro-inflammatory responses. The Mw-AmpB combination induced nitric oxide production, restored Th1 response, and significantly reduced parasite burden in wild type macrophages but not in IL-12-deficient macrophages indicating a pivotal role for IL-12 in the induction of host-protection by Mw and AmpB treatments. In addition, we observed that Mw alone or in combination with suboptimal dose of AmpB render protection against L. donovani infection in susceptible BALB/c mice. However, these treatments failed to render protection in IL-12-deficient mice in vivo which added further support that IL-12 played a central role in this chemo immunotherapeutic approach. Thus, we demonstrate a novel chemo-immunotherapeutic approach- Mw and AmpB crosstalk eliminating the parasite-induced immunosuppression and inducing collateral host-protective effects.</p>
},
  year = {2012},
  journal = {PloS one},
  volume = {7},
  pages = {e40265},
  issn = {1932-6203},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390375/pdf/pone.0040265.pdf},
  doi = {10.1371/journal.pone.0040265},
  language = {eng},
}