Chowdhury, B.P. and Bandyopadhyay, S and Das, S. and Majumder , S. and Jha, M.K. and Majumder , S.B. and Saha, B. and Majumder , S. (2015) The host-protective effect of arabinosylated lipoarabinomannan against Leishmania donovani infection is associated with restoration of IFN-γ responsiveness. PLoS One, 10 (2).

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Abstract

Visceral leishmaniasis (VL), which is endemic as a major infectious disease in the tropical and subtropical countries, is caused by a protozoan parasite Leishmania donovani. At present, restricted treatment options and lack of vaccines intensify the problem of controlling VL. Therefore, finding a novel immunoprophylactic or therapeutic principle is a pressing need. Here, we report that arabinosylated lipoarabinomannan (Ara-LAM), a TLR2-ligand isolated from Mycobacterium smegmatis, exhibits a strong immunomodulatory property that conferred protection against L. donovani infection. Although, Ara-LAM modulates TLR2 and MAPK signaling, it is not known whether Ara-LAM involves IFN-γ signaling for effective parasite clearance. Because, it is reported that IFN-γ signaling, a principle mediator of NO generation and macrophage and Tcell activation, is hampered during leishmanial pathogenesis. Ara-LAM increases IFN-γ receptor expression and potentiates IFN-γ receptor signaling through JAK-STAT pathway. Moreover, Ara-LAM reciprocally modulates IRF4 and IRF8 expression and reinstates anti-leishmanial Th1 response that eventuates in significantly reduced parasite load in spleen and liver of L. donovani-infected BALB/c mice. IFN-γRα silencing resulted in the suppression of these host-protective mechanisms affected by Ara-LAM. Thus, Ara-LAM-mediated restoration of IFN-γ responsiveness is a novel immuno-modulatory principle for protection against L. donovani susceptible host.

Item Type:	Article
Additional Information:	This is Open Access article for full text click above web link
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	28 Apr 2015 05:36
Last Modified:	26 May 2016 08:30
URI:	http://nccs.sciencecentral.in/id/eprint/152

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