Leishmania TRL Interaction Dictates the Fate of the Parasite The Role of TLR2

Abstract

Pathogen and host immune cells challenge each other via regulating the signaling pathways and newlineconsequently regulating the host defense response and simultaneously priming the host immune newlinesystem. Protozoan parasite Leishmania donovani like any other pathogen exploits the host cellular newlinemechanisms to harness protection via an interesting biological mechanism of deception. Pathogen newlineRecognition Receptor (PRR) like Toll-like Receptor (TLRs) of the antigen-presenting cells responsible newlinefor host protection can also be used by the pathogen to successively regulate their signaling pathway to newlinemodulate the inflammatory response of the cells. The rate of success in such an endeavor depends on newlinefew factors and any blocking or inhibition of those factors may alter the course of inflammatory newlineresponse.Considering previous reports, this regulation of the TLR signaling pathways by Leishmania newlinedonovani has not been extensively studied as much as the pattern of final changes in inflammatory newlineresponses, and the informations so far also lack a detailed understanding of L.donovani surface newlineantigenic molecule lipophosphoglycan (LPG)-TLR2 relationship. newlineOur study focuses on the macrophage polarization status with the advent of L.donovani infection, newlinefollowed by molecular investigation on macrophage s TLR2 cytoplasmic domain functional newlinedimerization with TLR1 and TLR6 and the impact of such differential pattern of interactions on the newlinedifferential signaling of TLR2. Futher, we explored the influence of infection on the TLR2 signaling newlinepathway and the factors switching the pathway to pro-parasitic response. Finally, we deduce the newlinepurpose of the pathogen surface antigenic molecule lipophosphoglycan in the pathogen APC newlineinteraction and infection establishment. newlineOur in-vivo study observes a gradual increase in M2 type macrophage polarization in the course of newlineL.donovani infection development. The computational study using molecular docking and molecular newlinedynamics reveals that, the TLR2 differentially interact with TLR1 and TLR6 which is actively similar newlinei