Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN-γ-induced gene expression by TLR2-dependent and independent pathways
Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN-γ-induced gene expression by TLR2-dependent and independent pathways
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DOI：
10.1089/jir.2006.26.548
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发表时间：
2006-08-01
影响因子：
2.3
通讯作者：
Zwilling, Bruce S.
中科院分区：
文献类型：
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作者：
Lafuse, William P.;Alvarez, Gail R.;Zwilling, Bruce S.
分枝杆菌感染的巨噬细胞对干扰素-γ（IFN-γ）的反应较差，导致IFN-γ诱导的基因表达降低。在本研究中，我们研究了小鼠RAW 264.7巨噬细胞中结核分枝杆菌和四种不同的鸟分枝杆菌菌株对IFN-γ诱导的基因表达的抑制。γ辐照M.结核抑制一组六种不同IFN-γ诱导基因的mRNA表达。所有四个M。禽流感病毒株完全抑制IFN-γ诱导的MHC Ⅱ类A α和E β mRNA的表达。然而，血清型1的Mac 101菌株抑制IFN-γ诱导IFN调节因子-1（IRF-1）和鸟苷酸结合蛋白-1（GBP-1）mRNA的程度大于其它M.禽流感病毒株，其为血清型2。在这项研究中，我们还表明，分枝杆菌抑制基因表达的Toll样受体2（TLR 2）依赖和独立的途径。M.在TLR 2（-/-）小鼠巨噬细胞中，avium减少但未完全阻断。IFN-γ诱导的基因表达在表达显性阴性TLR 2或髓样分化因子88（MyD 88）的RAW264.7细胞中也被分枝杆菌抑制，进一步表明存在独立于TLR 2和MyD 88的途径。这些数据表明，分枝杆菌抑制IFN-γ诱导的基因表达的多种途径，涉及TLR 2和非TLR受体。
Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN-gamma induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II A alpha and E beta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(-/-) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominant-negative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.