Selvakumar Tharini A, Bhushal Sudeep, Kalinke Ulrich, Wirth Dagmar, Hauser Hansjörg, Köster Mario, Hornef Mathias W
Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, Hannover, Germany.
Research Group Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
Front Immunol. 2017 Oct 16;8:1302. doi: 10.3389/fimmu.2017.01302. eCollection 2017.
Type I (α and β) and type III (λ) interferons (IFNs) induce the expression of a large set of antiviral effector molecules their respective surface membrane receptors. Whereas most cell types respond to type I IFN, type III IFN preferentially acts on epithelial cells and protects mucosal organs such as the lung and gastrointestinal tract. Despite the engagement of different receptor molecules, the type I and type III IFN-induced signaling cascade and upregulated gene profile is thought to be largely identical. Here, we comparatively analyzed the response of gut epithelial cells to IFN-β and IFN-λ and identified a set of genes predominantly induced by IFN-λ. We confirm the influence of epithelial cell polarization for enhanced type III receptor expression and demonstrate the induction of predominantly IFN-λ-induced genes in the gut epithelium . Our results suggest that IFN-λ targets the epithelium and induces genes to adjust the antiviral host response to the requirements at mucosal body sites.
I型(α和β)和III型(λ)干扰素(IFN)通过它们各自的表面膜受体诱导大量抗病毒效应分子的表达。虽然大多数细胞类型对I型干扰素产生反应,但III型干扰素优先作用于上皮细胞,并保护诸如肺和胃肠道等粘膜器官。尽管涉及不同的受体分子,但I型和III型干扰素诱导的信号级联反应和上调的基因谱被认为在很大程度上是相同的。在这里,我们比较分析了肠道上皮细胞对IFN-β和IFN-λ的反应,并鉴定出一组主要由IFN-λ诱导的基因。我们证实上皮细胞极化对增强III型受体表达的影响,并证明在肠道上皮中主要诱导IFN-λ诱导的基因。我们的结果表明,IFN-λ作用于上皮细胞并诱导基因,以根据粘膜部位的需求调整抗病毒宿主反应。