结核分枝杆菌诱导巨噬细胞产生的条件培养基对γ-干扰素信号转导系统的抑制作用

Inhibitory effect of Mycobacterium tuberculosis induced condition medium on macrophage response to IFN-γ

目的:探讨结核分枝杆菌对γ-干扰素(IFN-γ)信号转导的作用。方法:体外分离及培养人和鼠类巨噬细胞,感染结核分枝杆菌并收集条件培养基(Mtb-CM);流式细胞仪测定Mtb-CM对人及鼠巨噬细胞的表面标志FcγRI(CD64)和组织相容性Ⅱ类分子(MHCⅡ)的表达。结果:与Mtb-CM共同培养的人巨噬细胞 FcγRI的表达明显低于未加Mtb-CM的对照组(P<0．05);同样,与Mtb—CM共同培养的鼠巨噬细胞MHCⅡ的表达亦明显低于对照组(P<0．05);加入抗IL-6抗体的Mtb—CM可使巨噬细胞对IFN-γ的应答反应提高,其表面标志的表达明显高于未加IL-6抗体的对照组(P<0．05)。结论:结核分枝杆菌诱导巨噬细胞产生的Mtb—CM 可抑制由IFN-γ介导的巨噬细胞表面标志的表达;Mtb—CM中所含的刺激因子可能为IL-6,揭示了IL-6在结核菌感染中的新作用。

Objective Objective To study the effect of Mycobacterium tuberculosis （Mtb） on IFN-γ signaling pathway in macrophages. Methods Humans and mice macrophages were isolated and infected by Mtb, condition medium were collected after a few days culture; Macrophage surface expression of FcγRI （human） or MHC Ⅱ （mouse） was measured by flow cytometry to explore the effect of condition medium on macrophage response to IFN-γ. Results Surface expression of FcγRI in human macrophages cultured in condition medium was significantly decreased compared to those without condition medium （p〈0. 05）;Similarly, surface expression of MHC Ⅱ in mouse macrophages cultured in the condition medium was significantly decreased compared to those without condition medium （P〈0. 05） ; Condition medium cultured with anti IL-6 antibody improved macrophage response to IFN-γ; Surface expression of MHC Ⅱ in mouse macrophages cultured in condition medium with anti IL-6 antibody was significantly increased compared to those cultured in condition medium alone （P〈 0. 05）. Conclusion Mtb induced condition medium can inhibit macrophage surface expression of FcTRI or MHC initiated by IFN-γ At meanwhile, the results also show that IL-6 may play an important role in condition medium which can inhibits macrophage response to IFN-γ, and indicate that IL-6 may have a novel function in the Mtb infection.