Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

Diverse intracellular pathogens activate type III interferon expression from peroxisomes.
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各种细胞内病原体激活过氧化物酶体的III型干扰素表达。

DOI:
10.1038/ni.2915
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发表时间:
2014-08
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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I型干扰素(IFN)应答被认为是控制哺乳动物病毒感染的主要手段。尽管有这种观点,但在缺乏I型干扰素的情况下,一些病原体会激活抗病毒反应。控制I型干扰素非依赖性反应的机制尚不明确。我们发现RIG-I样受体(RLRs)在多种人类细胞类型中诱导III型IFN表达,并确定了调节I型和III型IFN表达的差异因子。我们发现过氧化物酶体是启动III型IFN表达的主要位点,并揭示了肠上皮细胞分化过程上调过氧化物酶体的生物发生,并促进人类细胞中III型IFN的强烈反应。这些发现强调了先天免疫和细胞生物学之间的相互联系。
Type I Interferon (IFN) responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of Type I IFNs. The mechanisms controlling Type I IFN-independent responses are undefined. We have found that RIG-I like Receptors (RLRs) induce Type III IFN expression in a variety of human cell types, and identified factors that differentially regulate Type I and III IFN expression. We identified peroxisomes as a primary site that initiates Type III IFN expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust Type III IFN responses in human cells. These findings highlight the interconnections between innate immunity and cell biology.
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