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Modulation of Interferon-gamma Receptor Expression During Infection with Chlamydia psittaci 6BC and Its Influence on Indoleamine 2,3-dioxygenase

Shirey, Kari Ann
http://rave.ohiolink.edu/etdc/view?acc_num=miami1140715510

Abstract Details

2006, Doctor of Philosophy, Miami University, Microbiology.
Interferon-gamma (IFNγ) induces indoleamine dioxygenase (IDO), which effectively inhibits the growth of intracellular Chlamydia in vitro. Furthermore, tumor necrosis factor-alpha (TNFα) and interleukin-1 (IL-1) synergistically increase IFN-induced, anti-chlamydial IDO activity. The mechanism of synergistic IDO activity is multifactorial. While one mechanism is the nuclear factor-κB (NF-κB)-dependent increase in interferon regulatory factor-1 (IRF-1) activation, increased expression of IFNγ receptors (IFNγR), could also enhance IDO activation. It was found that IFNγR expression was up-regulated in epithelial cells upon stimulation with IL-1, also through the transactivation of NF-κB. This increase in receptor expression was shown to enhance IDO activity by increasing activation of the transcription factor signal transducer and activator of transcription-1 (STAT-1). Moreover, Chlamydia was found to significantly increase IFNγR expression in HeLa cells, even when inactivated, suggesting that chlamydial antigens and not infection up-regulate cytokine receptor expression. Cytokine receptor increase was found to be independent of cytokine secretion as supernatants from infected cells failed to increase IFNγR expression. The component of Chlamydia responsible for stimulating the cell to up-regulate cytokine receptor expression is heat stable; receptors increased occurred upon stimulation with Chlamydia inactivated at 100°C. The mechanism by which Chlamydia increases receptor expression requires stimulation of the Toll-like receptors (TLR). While cells either TLR2 or TLR4+MD2 increased IFNγ receptor expression, cells not possessing TLRs were unresponsive. Similar to IL-1, Chlamydia required TLR-mediated NF-κB activation to enhance IFNγR expression. However, unlike stimulation with cytokine, no increase in IDO induction was observed. This effect is not due to the inability of IFNγ to bind to the newly expressed receptors, but rather the impairment in signaling of these receptors. No increase in phosphorylated STAT-1 could be detected in infected cells suggesting that the JAK/STAT pathway was affected.
Joseph Carlin (Advisor)
185 p.

Recommended Citations

Citations

  • Shirey, K. A. (2006). Modulation of Interferon-gamma Receptor Expression During Infection with Chlamydia psittaci 6BC and Its Influence on Indoleamine 2,3-dioxygenase [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1140715510

    APA Style (7th edition)

  • Shirey, Kari Ann. Modulation of Interferon-gamma Receptor Expression During Infection with Chlamydia psittaci 6BC and Its Influence on Indoleamine 2,3-dioxygenase. 2006. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1140715510.

    MLA Style (8th edition)

  • Shirey, Kari Ann. "Modulation of Interferon-gamma Receptor Expression During Infection with Chlamydia psittaci 6BC and Its Influence on Indoleamine 2,3-dioxygenase." Doctoral dissertation, Miami University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=miami1140715510

    Chicago Manual of Style (17th edition)

miami1140715510
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© 2006, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.