| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 92 === Type I interferons (IFNs) are critical cytokines for innate immunity to combat viral and bacterial infections. It has been well documented that signal transducer and activator of transcription (STAT) proteins, such as STAT1, STAT2, and STAT3, are activated upon IFN-a/b stimulation. While essential roles of STAT1 and STAT2 in IFN-a/b-mediated antiviral responses are demonstrated in gene targeting mice, the role of STAT3 remains unclear. Using macrophages derived from STAT3-deficient mice, the role of STAT3 in IFN-a/b-mediated antiviral responses is investigated. An impaired induction of antivirus-associated genes, such as interferon regulatory factor 1 (IRF1), interferon regulatory factor 7 (IRF7), and oligoadenylate synthetase (OAS) was observed in bone marrow-derived macrophage (BMM) and peritoneal macrophage (PM) of STAT3KO mice compared to those of control mice in response to IFN-a/b. Likewise, induction of IFN-a and PKR genes was also reduced in STAT3KO BMM in response to poly (I:C), a chemical reagent mimicking viral infection. The effect of impaired IFN-a response of STAT3KO macrophage on antiviral response was further tested by infecting macrophage with encephalomyocarditis virus (EMCV). Under suboptimal infection conditions (reduced-serum conditions), STAT3KO BMM displayed an enhanced survival rate after EMCV infection without pretreatment of IFN-a. However, the viral titer of EMCV-infection control or STAT3KO macrophage was comparable. Under optimal infection conditions (high-serum conditions), an enhanced cytopathic effect (CPE) and viral titer were observed in PM of STAT3KO mice with or without pretreatment of different doses of IFN-a. Taken together, these results suggest an important and yet previously uncharacterized role of STAT3 in IFN-a-mediated antiviral responses in macrophage.
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