TAILIEUCHUNG - Báo cáo khoa học: Mycobacterium tuberculosis secreted antigen (MTSA-10) modulates macrophage function by redox regulation of phosphatases

Macrophages are the primary host cells forMycobacterium tuberculosis (Mtb). Although macrophages can mount a strong inflammatory response to dispose of invading microbial pathogens, the immune dysfunction of the Mtb-infected macrophage constitutes the hallmark of mycobacterial patho-genesis. | ỊFEBS Journal Mycobacterium tuberculosis secreted antigen MTSA-10 modulates macrophage function by redox regulation of phosphatases Sandip K. Basu Dhiraj Kumar Dinesh K. Singh Niladri Ganguly Zaved Siddiqui Kanury V. S. Rao and Pawan Sharma Immunology Group InternationalCentre for Genetic Engineering and Biotechnology ICGEB Campus Aruna Asaf Ali Marg New Delhi India Keywords macrophage dysfunction MTSA-10 Mycobacterium tuberculosis protein phosphatases reactive oxygen species Correspondence P. Sharma InternationalCentre for Genetic Engineering and Biotechnology ICGEB Campus Aruna Asaf Ali Marg New Delhi 110067 India Fax 91 11 26162316 Tel 91 11 26176680 E-mail pawan37@ Received 7 July 2006 revised 6 October 2006 accepted 17 October 2006 doi Macrophages are the primary host cells for Mycobacterium tuberculosis Mtb . Although macrophages can mount a strong inflammatory response to dispose of invading microbial pathogens the immune dysfunction of the Mtb-infected macrophage constitutes the hallmark of mycobacterial pathogenesis. A 10-kDa Mtb secretory antigen MTSA-10 encoded by ORF Rv3874 is one of the predominant members of the region of difference 1 locus of Mtb genome that has been strongly implicated in mycobacterial virulence. In this study we investigated the possible role of MTSA-10 in modulating the macrophage dysfunction in a mouse macrophage cell line . We found that recombinant MTSA-10 caused extensive protein dephosphorylation in cells as revealed by two-dimensional gel electrophoresis analysis. We also observed that MTSA-10 treatment downregu-lated the reactive oxygen species levels in the cells leading to activation of cellular protein phosphatases putatively responsible for the dephosphorylation phenomenon. This implied a direct role of MTSA-10 in the disruption of host cell signaling resulting in downregulation of transcription of several genes essential for macrophage function. Mycobacterium .

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