arabinosylated lipoarabinomannan skews th2 phenotype towards th1 during leishmania infection by chromatin modification involvement of mapk signalingarabinosylated lipoarabinomannan倾斜th2表型向th1在利什曼虫感染的染色质修饰参与mapk信号.pdfVIP

Arabinosylated Lipoarabinomannan Skews Th2 Phenotype towards Th1 during Leishmania Infection by Chromatin Modification: Involvement of MAPK Signaling 1 1 1 1 1 Parna Bhattacharya , Gaurav Gupta , Saikat Majumder , Anupam Adhikari , Sayantan Banerjee , Kuntal 1 1 2 1 2 Halder , Suchandra Bhattacharya Majumdar , Moumita Ghosh , Shubho Chaudhuri , Syamal Roy , Subrata Majumdar1* 1 Division of Molecular Medicine, Bose Institute, Kolkata, India, 2 Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India Abstract The parasitic protozoan Leishmania donovani is the causative organism for visceral leishmaniasis (VL) which persists in the host macrophages by deactivating its signaling machinery resulting in a critical shift from proinflammatory (Th1) to an anti- inflammatory (Th2) response. The severity of this disease is mainly determined by the production of IL-12 and IL-10 which could be reversed by use of effective immunoprophylactics. In this study we have evaluated the potential of Arabinosylated Lipoarabinomannan (Ara-LAM), a cell wall glycolipid isolated from non pathogenic Mycobacterium smegmatis, in regulating the host effector response via effective regulation of mitogen-activated protein kinases (MAPK) signaling cascades in Leishmania donovani infected macrophages isolated from BALB/C mice. Ara-LAM, a Toll-like receptor 2 (TLR2) specific ligand, was found to activate p38 MAPK signaling along with subsequent abrogation of extracellular signal–regulated kinase (ERKs) signaling. The use of pharmacological inh