Open AccessMycobacterium bovis bacillus Calmette‐Guérin infection promotes SOCS induction and inhibits IFN‐γ‐stimulated JAK/STAT signaling in J774 macrophages
Author(s) -
Imai Kenichi,
KuritaOchiai Tomoko,
Ochiai Kuniyasu
Publication year - 2003
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1016/s0928-8244(03)00231-1
Subject(s) - biology , mycobacterium bovis , signal transduction , microbiology and biotechnology , cytokine , stat , mycobacterium tuberculosis , stat1 , mycobacterium , macrophage , immunology , bacteria , tuberculosis , stat3 , medicine , biochemistry , genetics , pathology , in vitro
The resurgence in mycobacterial infection worldwide has led to renewed attention to the pathogenesis of Mycobacterium species. Although interferon‐γ (IFN‐γ) is a principal mediator of macrophage activation, macrophages infected with Mycobacterium are poor in response at the cytokine. However, the molecular mechanisms underlying mycobacterial infection remain unclear. The purpose of this study was to elucidate the mechanism of the poor response to IFN‐γ in mycobacterial infection. Our data clearly demonstrate that this is due to induction of suppressor of cytokine signal (SOCS) negative regulators of IFN‐γ signal transduction that closely correlates with the inhibition of JAK/STAT signaling and gene expression stimulated by IFN‐γ. Mycobacterium bovis bacillus Calmette‐Guérin infection induces the production of SOCS‐1 and SOCS‐3 in murine J774 macrophages. The level of SOCS‐1 mRNA increased 1 h and reached a maximum 3 h after the addition of the bacteria. SOCS‐3 mRNA expression appeared as early as 1 h after the infection. We also observed that trehalose 6,6′‐dimycolate/cord factor, a major component of the Mycobacterium tuberculosis cell wall, induces expression of SOCS and inhibits IFN‐γ‐stimulated phosphorylation of STAT1 extensively in the cells. The results in this study suggest that a molecular mechanism of mycobacterial infection affects the unresponsiveness to IFN‐γ in the subsequent growth and spread of macrophages.