03124nas a2200517   4500000000100000008004100001653001900042653001200061653002500073653002000098653001400118653001800132653001900150653002400169653002800193653001000221653003200231653002600263653001600289653000900305653000900314653002400323653001900347653001700366653003200383653002800415653001100443653001400454100001500468700001200483700001500495700001500510700002000525700001900545700001300564700001300577700001600590700001100606700001500617245015400632856007800786300001100864490000600875520171100881022001402592       2012                            d10aAmphotericin B10aAnimals10aAntiprotozoal Agents10aCells, Cultured10aCytokines10aImmunotherapy10aInterleukin-1210aLeishmania donovani10aLeishmaniasis, Visceral10aLiver10aMAP Kinase Signaling System10aMacrophage Activation10aMacrophages10aMale10aMice10aMice, Inbred BALB C10aMice, Knockout10aNitric Oxide10aNontuberculous Mycobacteria10aReactive Oxygen Species10aSpleen10aTh1 Cells1 aAdhikari A1 aGupta G1 aMajumder S1 aBanerjee S1 aBhattacharjee S1 aBhattacharya P1 aKumari S1 aHaldar S1 aMajumdar SB1 aSaha B1 aMajumdar S00aMycobacterium indicus pranii (Mw) re-establishes host protective immune response in Leishmania donovani infected macrophages: critical role of IL-12.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390375/pdf/pone.0040265.pdf  ae402650 v73 a<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>
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