Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract.
Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract.
复制标题
DOI：
10.4049/jimmunol.1102764
复制
发表时间：
2012-02-15
期刊：
影响因子：
--
通讯作者：
Slaven JE
中科院分区：
文献类型：
--
作者：
Johnson RM;Kerr MS;Slaven JE
泌尿生殖道沙眼衣原体血清型主要在生殖道上皮中复制。这种组织向性对宿主防御和疫苗开发提出了独特的挑战。利用小鼠衣原体模型的研究表明，CD 4 T细胞对于清除生殖道感染至关重要。体外研究表明，CD 4 T细胞通过上调上皮iNOS转录和一氧化氮产生来终止感染。然而，这种机制并不重要，因为iNOS缺陷小鼠通常会清除感染。我们最近发现，衣原体特异性CD 4 T细胞克隆的一个子集可以终止复制上皮细胞使用iNOS-独立的机制，需要T细胞脱粒。我们使用微阵列来比较iNOS依赖性和iNOS非依赖性CD 4 T细胞克隆。Plac 8通过具有iNOS非依赖性机制的克隆差异表达。Plac 8缺陷型小鼠感染清除延迟，用iNOS抑制剂N-单甲基-L-精氨酸治疗的Plac 8缺陷型小鼠在8周内基本上不能解决生殖道感染。这些结果表明，有两个独立的和冗余的T细胞清除C。小鼠生殖道感染;一个依赖于iNOS，另一个依赖于Plac 8。虽然T细胞亚群通常由细胞因子谱定义，但可能存在效应子功能的重要细分，在这种情况下为CD 4Plac 8。
Chlamydia trachomatis urogenital serovars replicate predominately in genital tract epithelium. This tissue tropism poses a unique challenge for host defense and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical for clearing genital tract infections. In vitro studies have shown that CD4 T cells terminate infection by up regulating epithelial iNOS transcription and nitric oxide production. However, this mechanism is not critical as iNOS-deficient mice clear infections normally. We recently showed that a subset of Chlamydia-specific CD4 T cell clones could terminate replication in epithelial cells using an iNOS-independent mechanism requiring T cell degranulation. We advance that work using microarrays to compare iNOS-dependent and iNOS-independent CD4 T cell clones. Plac8 was differentially expressed by clones having the iNOS-independent mechanism. Plac8-deficient mice had delayed clearance of infection, and Plac8-deficient mice treated with the iNOS-inhibitor N-monomethyl-L-arginine were largely unable to resolve genital tract infections over 8 weeks. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections; one dependent on iNOS, the other dependent on Plac8. While T cells subsets are routinely defined by cytokine profiles, there may be important subdivisions by effector function, in this case CD4Plac8.
登录
查看更多内容
影响因子：
6.4
作者：
Igietseme, JU
通讯作者：
Igietseme, JU
DOI：
10.4049/jimmunol.1002596
发表时间：
2010-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jayarapu K;Kerr M;Ofner S;Johnson RM
通讯作者：
Johnson RM
影响因子：
4.4
作者：
Morrison, SG;Morrison, RP
通讯作者：
Morrison, RP
影响因子：
4.4
作者：
Ledford, Julie G.;Kovarova, Martina;Koller, Beverly H.
通讯作者：
Koller, Beverly H.
影响因子：
3.1
作者：
Li, Weidang;Murthy, Ashlesh K.;Arulanandam, Bernard P.
通讯作者：
Arulanandam, Bernard P.