Necrostatin-1抑制白色念珠菌诱导的巨噬细胞自噬而影响免疫应答

Necrostatin-1 affects macrophage's immune response to Candida albicans by inhibiting autophagy

随着现代医疗技术的发展,人口老龄化加剧,抗生素滥用等降低人体免疫力的因素越来越多,使得由白色念珠菌Candida albicans感染引起的疾病发生率越来越高。本研究通过使用程序性坏死的选择性抑制剂Necrostatin-1,初步探索了细胞自噬和程序性死亡在巨噬细胞抗白色念珠菌感染中的作用。研究表明:细胞自噬参与了白色念珠菌侵染巨噬细胞的过程,而Necrostatin-1可能通过抑制白色念珠菌感染引起的自噬促进IL-6的表达,并抑制TNF-α(肿瘤坏死因子α)的表达,进而对白色念珠菌引起的天然免疫反应产生影响。细胞自噬在抗真菌感染方面的研究已有报道,而程序性坏死在抗真菌感染方面的研究鲜有报道,同时Necrostatin-1在巨噬细胞抗白色念珠菌感染中的作用尚未见报道。本研究对白色念珠菌侵染机理的探索具有一定的意义。

Diseases caused by Candida albicans infection have been growing serious with the development of modern medical technology and abuse of antibiotics, while the increase of aged tendency of population also contributes to this problem. In this study, we found that the white phase of C. albicans can induce autophagy in the macrophage cells ignoring whether it is alive or heat-killed. At the same time, necrostatin-1, a selective inhibitor of necroptosis, can induce autophagy too. However, necrostatin-1 can attenuate the autophagy induced by white type C. albicans when treated with both of them. The expression of IL-6 was up-regulated, while TNF-α is down-regulated. All the results indicate that autophagy participates in the process of C.albicans invasion of macrophage cells. Autophagy has been reported to take part in the regulation of the fungistatic activity by immune system. Necroptosis, which belong to the three programmed cell death type, also participate in the regulation of immune system. Besides, it remains almost unknown whether necrostatin-1 has impacts on Candida albicans infection. Therefore our results have a contribution to the infection mechanism of C. albicans.