Arabinosylated lipoarabinomannan (Ara-LAM) mediated intracellular mechanisms against tuberculosis infection: Involvement of protein kinase C (PKC) mediated signaling. Issue 2 (March 2015)

• Record Type: Journal Article
• Authors: Das, Shibali; Bhattacharjee, Oindrila; Goswami, Avranil; Pal, Nishith K.; Majumdar, Subrata
• Is Part Of: Tuberculosis. Volume 95:Issue 2(2015)
• Page Start: 208
• Page End: 216
• Publication Date: 2015-03
• Subjects: 616.995
• DOI: 10.1016/j.tube.2014.11.007
• Languages: English
• ISSNs: 1472-9792

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Summary</title> <sec> <p id="abspara0010">Tuberculosis causes severe immunosuppression thereby ensuring the loss of the host protective immune responses. During <italic>Mycobacterium tuberculosis</italic> infection, the pathogen modulates TLR-2 receptor down-stream signaling, indicating the possible involvement of TLR-2 in the regulation of the host immune response. Moreover, different PKC isoforms are also involved in the course of infection. Arabinosylated lipoarabinomannan (Ara-LAM) possesses immuno-modulatory properties which induce the pro-inflammatory responses via induction of TLR-2-mediated signaling. Here, we found that pretreatment of <italic>M. tuberculosis</italic>-infected macrophages with Ara-LAM caused a significant increase in the conventional PKC expression along with their active association with TLR-2. This association activated the TLR-2 -mediated downstream signaling, facilitating the activation of MAP kinase P38. All these events culminated in the up-regulation of proinflammatory response, which was abrogated by treatment with PKC-α and P38 inhibitors. Moreover, pretreatment of macrophages with Ara-LAM abrogated the IL-10 production while restored MHC-II expression in the infected macrophages. This study demonstrates that Ara-LAM confers protection against tuberculosis via TLR-2/PKC signaling crosstalk which is responsible for the induction of host protective immune response against tuberculosis.</p> </sec> </abstract>