Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma.
Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma.
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DOI：
10.1038/s41598-018-26765-y
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发表时间：
2018-05-31
影响因子：
4.6
通讯作者：
Aiyar A
中科院分区：
文献类型：
--
作者：
Ibana JA;Sherchand SP;Fontanilla FL;Nagamatsu T;Schust DJ;Quayle AJ;Aiyar A
细胞内细菌病原体沙眼衣原体是色氨酸营养缺陷型。因此，干扰素γ（IFNγ）诱导宿主色氨酸分解代谢酶吲哚胺-2，3-二氧合酶-1（IDO 1）是抗衣原体感染的主要保护性反应之一。然而，尽管存在强有力的IFNγ应答，活性和复制C.在妇女的宫颈分泌物中可以检测到沙眼。我们假设一个主要的C。沙眼衣原体感染可能逃避IFNγ应答，这种细胞因子的保护作用是由于其激活旁观者细胞中的色氨酸催化剂。为了验证这一假设，我们开发了一种新的方法来分离暴露于C。将沙眼衣原体分离到纯的活感染细胞和旁观者细胞群中，并应用该技术来区分IFNγ对感染细胞和旁观者细胞的作用。我们的研究结果表明，IDO 1的保护性诱导在原发性感染细胞内被特异性抑制，因为衣原体在IFNγ暴露后减弱了活化的STAT 1的核输入，而不影响STAT 1水平或磷酸化。重要的是，IFNγ介导的IDO 1活性诱导在旁观者细胞中不受阻碍。因此，IDO 1介导的色氨酸催化剂在这些细胞中起作用，将这些旁观者细胞转化为第二C.沙眼感染
The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and replicating C. trachomatis can be detected in cervical secretions of women. We hypothesized that a primary C. trachomatis infection may evade the IFNγ response, and that the protective effect of this cytokine results from its activation of tryptophan catabolism in bystander cells. To test this hypothesis, we developed a novel method to separate a pool of cells exposed to C. trachomatis into pure populations of live infected and bystander cells and applied this technique to distinguish between the effects of IFNγ on infected and bystander cells. Our findings revealed that the protective induction of IDO1 is suppressed specifically within primary infected cells because Chlamydia attenuates the nuclear import of activated STAT1 following IFNγ exposure, without affecting STAT1 levels or phosphorylation. Critically, the IFNγ-mediated induction of IDO1 activity is unhindered in bystander cells. Therefore, the IDO1-mediated tryptophan catabolism is functional in these cells, transforming these bystander cells into inhospitable hosts for a secondary C. trachomatis infection.
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