Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma

Autor: Ashok Aiyar, Takeshi Nagamatsu, Shardulendra P. Sherchand, Francis L. Fontanilla, Danny J. Schust, Joyce A. Ibana, Alison J. Quayle
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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