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Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages
 
Creator Banerjee, Somenath
Bose, Dipayan
Chatterjee, Nabanita
Das, Subhadip
Chakraborty, Sreeparna
Das, Tanya
Das Saha, Krishna
 
Subject Infectious Diseases and Immunology
 
Description 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 preexposed 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
 
Date 2016
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2463/1/SCIENTIFIC_REPORTS__Volume__6______Article_Number__22335;2016.pdf
Banerjee, Somenath and Bose, Dipayan and Chatterjee, Nabanita and Das, Subhadip and Chakraborty, Sreeparna and Das, Tanya and Das Saha, Krishna (2016) Attenuated Leishmania induce pro-inflammatory mediators and influence leishmanicidal activity by p38 MAPK dependent phagosome maturation in Leishmania donovani co-infected macrophages. Scientific Reports, 6 (22335). 01p. -14p..
 
Relation http://dx.doi.org/10.1038/srep22335
http://www.eprints.iicb.res.in/2463/