Study On Immunological Function Of Host Protein Gab2 Involved In The Pathogenesis Of Tuberculosis

Tuberculosis is a chronic inflammatory disease caused by Mycobacteriumtuberculosis. Immune cells,such asT cells, macrophages and B cells play important roles in cellular immunity aganst tuberculosis.Gab2,a scaffolding adaptor protein.can mediate signal transduction from receptors of T cells, mononudear phagocytes,B cells and master cells etc. Especially,it is a negative regulatorin TCRsignaling pathways of T cells and Gab2 are critical to T cell proliferation and cytokine secretion. In this study, we examined the roles of Gab2 i n disease of tuberculosis.First, we found decreased mRNA level of Gab2 and its related molecules of Gab1 and SHP-2 in immune cells from pre anti-TB treatedindividuals with active tuberculosis compared to healthy controls.Importantly, the decreased level of Gab2 and SHR2 could gradually up-regulated after anti-TB treatment in a follow up study of tuberculosis patients during standard course anti-TB treatment period. Moreover, the up-regulated mRNA level could return to the normal level, when theirsputum smears test is clinical negative two months afterwards.Following, we examinedtherole of Gab2 in M.tuberculosisinfectionthrough Gab2-deficient mice. Eight weeks post infection.the lungs of the Gab2-deficient mice showed controlled bacterial colony forming units, mild pathological change, higher number of accumulated T cells, but lower macrophages andB cellsin inflammatory areas.lnflammatorycytokinessuch as GM-CSF,IL-2 and IL-6 were significantly decreased in serum of infected Gab2-deficuent mice,compared with infected wild type mice. Moreover, infected Gab2-deficient mice showed significant higher T-bet/GATA-3 mRNA ratioin spleen cells compared to infected wild type mice, suggesting a stronger Th1 biased immune response. Importantly,we also found mRNA and proten level of Gab2in lung tissue of wild type mice cut reduced during M.tuberculosis infection.Taken together, we herein addressed Gab2 play a role in disease of Tuberculosis..After M.tb infection, the host may regular Gab2 expression,decreased Gab2 level may be conductive to Th1 cells different on and inflammatory cytokines secretion.which will control bacterial proliferation and tissue damage. This study may provide a new perspective to understand mechanism underlying the protective immunity on tuberculosis and possi bi I ity i n a better therapeuti c strategy.