RETRACTED: Mycobacterium indicus pranii (Mw) re-establishes host protective immune response in Leishmania donovani infected macrophages: critical role of IL-12.
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.
Division of Molecular Medicine, Bose Institute, Kolkata, India.
Anupam
A
Adhikari
Gaurav
G
Gupta
Saikat
S
Majumder
Sayantan
S
Banerjee
Surajit
S
Bhattacharjee
Parna
P
Bhattacharya
Sangeeta
S
Kumari
Subhadra
S
Haldar
Suchandra Bhattacharyya
SB
Majumdar
Bhaskar
B
Saha
Subrata
S
Majumdar
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D007167:Immunotherapy; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D008099:Liver / Q000469:parasitology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009170:Nontuberculous Mycobacteria / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000981:Antiprotozoal Agents; D016207:Cytokines; D017382:Reactive Oxygen Species; D018664:Interleukin-12; D009569:Nitric Oxide; D000666:Amphotericin B