Hancková Miriam, Miháliková Lucia, Pastoreková Silvia, Betáková Tatiana
Biomedical Research Center, Slovak Academy of Sciences, Institute of Virology, Bratislava, Slovak Republic.
Biomedical Research Center, Slovak Academy of Sciences, Institute of Virology, Bratislava, Slovak Republic; Comenius University in Bratislava, Faculty of Natural Sciences, Department of Microbiology and Virology, Bratislava, Slovak Republic.
Cytokine. 2023 Apr;164:156138. doi: 10.1016/j.cyto.2023.156138. Epub 2023 Feb 14.
Macrophages are the most abundant cells in infected tissue and are involved in the clearing infection, and immunomodulation of the innate and adaptive immune response. NS80 virus of influenza A virus, which encodes only the first 80 aa of the NS1 protein, suppresses the immune host response and is associated with enhanced pathogenicity. Hypoxia promotes infiltration of peritoneal macrophages into the adipose tissue and production of cytokines. To understand the role of hypoxia in the regulation of immune response, macrophages were infected with A/WSN/33 (WSN) and NS80 virus, and transcriptional profiles of the RIG-I-like receptor signalling pathway and expression of cytokines were evaluated in normoxia and hypoxia. Hypoxia inhibited the proliferation of IC-21 cells, downregulated the RIG-I-like receptor signalling pathway, and inhibited transcriptional activity of IFN-α, IFN-β, IFN-ε, and IFN-λ mRNA in infected macrophages. While transcription of IL-1β and Casp-1 mRNAs were increased in infected macrophages in normoxia, hypoxia resulted in decreased transcription activity of IL-1β and Casp-1 mRNAs. Hypoxia significantly affected expression of the translation factors IRF4, IFN-γ, and CXCL10 involved in regulation of immune response and polarization of the macrophages. The expression of pro-inflammatory cytokines such as sICAM-1, IL-1α, TNF-α, CCL2, CCL3, CXCL12, and M-CSF was to a large extent affected in uninfected and infected macrophages cultivated in hypoxia. The NS80 virus increased the expression of M-CSF, IL-16, CCL2, CCL3, and CXCL12, especially under hypoxia. The results show that hypoxia may play an important role in peritoneal macrophage activation, regulates the innate and adaptive immune response, changes production of pro-inflammatory cytokines, promotes macrophage polarization, and could affect the function of other immune cells.
巨噬细胞是感染组织中数量最多的细胞，参与清除感染以及固有免疫和适应性免疫反应的免疫调节。甲型流感病毒的NS80病毒仅编码NS1蛋白的前80个氨基酸，可抑制宿主免疫反应并与致病性增强有关。缺氧促进腹膜巨噬细胞浸润到脂肪组织并产生细胞因子。为了解缺氧在免疫反应调节中的作用，将巨噬细胞用A/WSN/33（WSN）和NS80病毒感染，并在常氧和缺氧条件下评估RIG-I样受体信号通路的转录谱和细胞因子的表达。缺氧抑制IC-21细胞的增殖，下调RIG-I样受体信号通路，并抑制感染巨噬细胞中IFN-α、IFN-β、IFN-ε和IFN-λ mRNA的转录活性。在常氧条件下感染的巨噬细胞中IL-1β和Casp-1 mRNA的转录增加，而缺氧导致IL-1β和Casp-1 mRNA的转录活性降低。缺氧显著影响参与免疫反应调节和巨噬细胞极化的翻译因子IRF4、IFN-γ和CXCL10的表达。在缺氧条件下培养的未感染和感染的巨噬细胞中，促炎细胞因子如sICAM-1、IL-1α、TNF-α、CCL2、CCL3、CXCL12和M-CSF的表达在很大程度上受到影响。NS80病毒增加了M-CSF、IL-16、CCL2、CCL3和CXCL12的表达，尤其是在缺氧条件下。结果表明，缺氧可能在腹膜巨噬细胞激活中起重要作用，调节固有免疫和适应性免疫反应，改变促炎细胞因子的产生，促进巨噬细胞极化，并可能影响其他免疫细胞的功能。
