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Mannosylated Lipoarabinomannan (Man-LAM) produced by virulent Mycobacteria favors mycobacterial pathogenesis by the suppression of proinflammatory microenvironment within the host cell, but Arabinosylated Lipoarabinomannan (Ara- LAM) from avirulent mycobacteria evokes proinflammatory responses via induction of Toll like receptor-2 (TLR-2) mediated signaling.
In this study, we investigated whether Ara-LAM could stimulate the TLR-2 signaling and proinflammatory cytokine gene transcription during Man-LAM induced pathogenesis in murine macrophages. Ara-LAM pretreatment (3mg/ml) of Man-LAM treated macrophages induced association of TLR-2 with its downstream factor MyD88 and subsequently of MyD88 and IRAKs, leading to Ikk phosphorylation, IkB-a degradation, finally translocation and DNA binding of NF-kB. These events culminated in the up-regu- lation of cytokines TNF-a and IL-12, nitrite generation and iNOS mRNA expression, which could be abrogated significantly by treatment of macrophages with TLR-2 specific siRNA as well as anti-TLR-2 monoclonal antibody. Based on our observations, we strongly report the TLR-2 mediated protection of Ara-LAM during Man- LAM-mediated pathogenesis.
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