title: Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages.
abstract: Promastigote form of Leishmania, an intracellular pathogen, delays phagosome maturation and resides inside macrophages. But till date limited study has been done to manipulate the phagosomal machinery of macrophages to restrict Leishmania growth. Attenuated Leishmania strain exposed RAW 264.7 cells showed a respiratory burst and enhanced production of pro-inflammatory mediators. The augmentation of pro-inflammatory activity is mostly attributed to p38 MAPK and p44/42 MAPK. In our study, these activated macrophages are found to induce phagosome maturation when infected with pathogenic Leishmania donovani. Increased co-localization of carboxyfluorescein succinimidyl ester labeled pathogenic L. donovani with Lysosome was found. Moreover, increased co-localization was observed between pathogenic L. donovani and late phagosomal markers viz. Rab7, Lysosomal Associated Membrane Protein 1, Cathepsin D, Rab9, and V-ATPase which indicate phagosome maturation. It was also observed that inhibition of V-type ATPase caused significant hindrance in attenuated Leishmania induced phagosome maturation. Finally, it was confirmed that p38 MAPK is the key player in acidification and maturation of phagosome in attenuated Leishmania strain pre-exposed macrophages. To our knowledge, this study for the first time reported an approach to induce phagosome maturation in L. donovani infected macrophages which could potentiate short-term prophylactic response in future.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700032, India.
authors.forename: Somenath
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700032, India.
authors.forename: Dipayan
authors.initials: D
authors.lastname: Bose
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700032, India.
authors.forename: Nabanita
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700032, India.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Molecular Medicine, Bose Institute, Centenary Campus, P 1/12, C. I. T. Road, Scheme- VIIM, Kolkata - 700054, West Bengal, India.
authors.forename: Sreeparna
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Department of Molecular Medicine, Bose Institute, Centenary Campus, P 1/12, C. I. T. Road, Scheme- VIIM, Kolkata - 700054, West Bengal, India.
authors.forename: Tanya
authors.initials: T
authors.lastname: Das
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700032, India.
authors.forename: Krishna Das
authors.initials: KD
authors.lastname: Saha
mesh_terms: D000818:Animals; D018836:Inflammation Mediators / Q000378:metabolism; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology / Q000517:prevention & control*; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress; D010588:Phagosomes / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D014613:Vaccines, Attenuated; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D054332:Leishmaniasis Vaccines; D014613:Vaccines, Attenuated; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D025262:Vacuolar Proton-Translocating ATPases