Animal Genomics Lab, Animal Biotechnology Centre, ICAR-National Dairy Research Institute (NDRI), Karnal, HR 132001, India; Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, HR 139031, India.
Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, HR 139031, India.
Vet Immunol Immunopathol. 2024 Jun;272:110770. doi: 10.1016/j.vetimm.2024.110770. Epub 2024 May 4.
Interferon lambda (IFN-λ) is an important type III interferon triggered mainly by viral infection. IFN-λ binds to their heterodimeric receptors and signals through JAK-STAT pathways similar to type I IFN. In this study, we deduced the buffalo IFN-λ sequences through the polymerase chain reaction, and then studied IFN-λ's expression patterns in different tissues, and post induction with poly I:C and live MRSA using RT-qPCR. The full-length sequences of buffalo IFN-λ3, IFN-λ receptors, and a transcript variant of IFN-λ4 were determined. IFN-λ1 is identified as a pseudogene. Virus response elements and a recombination hotspot factor was observed in the regulatory region of IFN-λ. The IFN-λ3 expressed highest in lungs and monocytes but IFN-λ4 did not. The expression of Interferon Lambda Receptor 1 was tissue specific, while Interleukin 10 Receptor subunit beta was ubiquitous. Following poly I:C induction, IFN-λ3 expression was primarily observed in epithelial cells as opposed to fibroblasts, displaying cell type-dependent expression. The cytosolic RNA sensors were expressed highest in endometrial epithelial cells, whereas the endosomal receptor was higher in fibroblasts. 2',5'-oligoadenylate synthetase expressed higher in fibroblasts, myxoma resistance protein 1 and IFN-stimulated gene 56 in epithelial cells, displaying cell-specific antiviral response of the interferon stimulated genes (ISGs). The endometrial epithelial cells expressed IFN-λ3 after live S. aureus infection indicating its importance in bacterial infection. The induction of IFN-λ3 was S. aureus isolate specific at the same multiplicity of infection (MOI). This study elucidates the IFN-λ sequences, diverse expression patterns revealing tissue specificity, and specificity in response to poly I:C and bacterial stimuli, emphasising its crucial role in innate immune response modulation.
干扰素 λ(IFN-λ)是一种重要的 III 型干扰素,主要由病毒感染触发。IFN-λ 与它们的异二聚体受体结合,并通过类似于 I 型 IFN 的 JAK-STAT 途径信号传导。在这项研究中,我们通过聚合酶链反应推导出水牛 IFN-λ 序列,然后使用 RT-qPCR 研究了 IFN-λ 在不同组织中的表达模式,以及在用 poly I:C 和活 MRSA 诱导后的表达模式。确定了水牛 IFN-λ3、IFN-λ 受体和 IFN-λ4 的转录变体的全长序列。IFN-λ1 被鉴定为假基因。在 IFN-λ 的调控区域观察到病毒反应元件和重组热点因子。IFN-λ3 在肺部和单核细胞中表达最高,但 IFN-λ4 没有。干扰素 λ 受体 1 的表达具有组织特异性,而白细胞介素 10 受体亚基β则普遍存在。在用 poly I:C 诱导后,IFN-λ3 的表达主要在上皮细胞中观察到,而不是在成纤维细胞中,表现出细胞类型依赖性表达。细胞质 RNA 传感器在子宫内膜上皮细胞中表达最高,而内体受体在成纤维细胞中更高。2',5'-寡聚腺苷酸合成酶在成纤维细胞中表达更高,而 Myxoma 抗性蛋白 1 和 IFN 刺激基因 56 在上皮细胞中表达更高,表现出干扰素刺激基因(ISGs)的细胞特异性抗病毒反应。活金黄色葡萄球菌感染后子宫内膜上皮细胞表达 IFN-λ3,表明其在细菌感染中的重要性。IFN-λ3 的诱导在相同感染复数(MOI)下对金黄色葡萄球菌分离株具有特异性。这项研究阐明了 IFN-λ 序列、不同的表达模式揭示了组织特异性以及对 poly I:C 和细菌刺激的特异性,强调了其在先天免疫反应调节中的关键作用。