探究淋病奈瑟菌诱导的IDO1对CD4+T细胞分化的影响

Effects of Neisseria gonorrhoeae-induced IDO1 on CD4+T cell differentiation

目的探究吲哚胺2,3-双加氧酶-1(indoleamine 2,3-dioxygenase-1,IDO1)是否参与淋病奈瑟菌(Neisseria gonorrhoeae,Ng)感染病程,发挥有利于Ng感染的免疫调节作用。方法分离人外周血单个核细胞,体外诱导DC及鉴定DC表型;Western blot检测IDO1蛋白的表达量;检测Ng阳性患者分泌物中IDO1的mRNA表达水平;流式细胞术检测Ng阳性患者抗凝全血中Treg和髓源性抑制细胞(myeloid-derived suppressor cell,MDSC)的变化。结果研究发现Ng可诱导人DC产生IDO1,其诱导依赖于菌体的活力;Ng阳性患者的生殖道分泌物中IDO1的表达量明显高于健康人;外周血中MDSC和Treg的比例均高于健康人;结合相关文献报道,Treg可以诱导IDO1+的表达,而IDO1+反过来与MDSC一起促进新的Treg的分化,三者共同抑制CD4+T细胞的增殖,并共同作用参与免疫耐受。结论阐明免疫微环境中"IDO1-CD4+T细胞-免疫微环境"之间的免疫调控网络,为淋病免疫治疗提供新的靶点或治疗思路,以便更好地利用免疫治疗手段预防、控制淋病的发生、发展。

ObjectiveTo investigate whether indoleamine 2,3-dioxygenase-1(IDO1)is involved in Neisseria gonorrhoeae(Ng)infection and its immunomodulatory role in Ng infection.MethodsHuman peripheral blood mononuclear cells were induced to differentiate into DC in vitro.The phenotype of DC was identified.The expression of IDO1 was detected by Western blot.The expression of IDO1 at mRNA level in the secretions of Ng-positive patients was detected.Changes in Treg and myeloid-derived suppressor cell(MDSC)in the anticoagulant whole blood of Ng-positive patients were detected by flow cytometry.ResultsNg could induce human DCs to produce IDO1,which depended on the activity of Ng.The expression of IDO1 in the genital tract secretions of Ng-positive patients was significantly higher than that in healthy people.Besides,the proportions of MDSC and Treg in the peripheral blood of patients with Ng infection were higher than those in healthy people.Based on literature review,it was suggested that Treg could induce the expression of IDO1+,and IDO1+,in turn,together with MDSC,promoted the differentiation of new Treg,which inhibited the proliferation of CD4+T cells and was involved in immune tolerance.ConclusionsUnderstanding the immune regulatory network of"IDO1-CD4+T cells-immune microenvironment"in the immune microenvironment would provide new targets or thoughts for the immunotherapy of gonorrhea,so as to better use immunotherapy to prevent and control the occurrence and development of gonorrhea.