Mycobacterium avium Infection of Mouse Macrophages Inhibits IFN-γ Janus Kinase-STAT Signaling and Gene Induction by Down-Regulation of the IFN-γ Receptor

摘要: Macrophage activation is required to control the growth of intracellular pathogens. Recent data indicate that macrophages become functionally deactivated during mycobacterial infection. We studied macrophage deactivation by examining expression a panel IFN-γ-inducible genes and Janus Kinase (JAK)-STAT pathway in Mycobacterium avium- infected macrophages. Reduced genes—MHC class II gene Eβ; MHC transactivator; IFN regulatory factor-1; Mg21, coding for GTP-binding protein—was observed M. Decreased tyrosine phosphorylation DNA binding activity STAT1 stimulated with IFN-γ was observed. Tyrosine JAK1, JAK2, IFN-γRα also reduced cells. Northern Western blot analyses showed down-regulation IFN-γR α- β-chain mRNA protein occurred The inhibition were time dependent 4 h infection 8 inhibition. These findings suggest avium inhibits induction mouse down-regulating IFN-γR, resulting IFN-γRα, STAT1.