Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Mediators Inflamm. 2019 Oct 9;2019:4964239. doi: 10.1155/2019/4964239. eCollection 2019.
Human metapneumovirus (HMPV) may cause severe respiratory disease. The early innate immune response to viruses like HMPV is characterized by induction of antiviral interferons (IFNs) and proinflammatory immune mediators that are essential in shaping adaptive immune responses. Although innate immune responses to HMPV have been comprehensively studied in mice and murine immune cells, there is less information on these responses in human cells, comparing different cell types infected with the same HMPV strain. The aim of this study was to characterize the HMPV-induced mRNA expression of critical innate immune mediators in human primary cells relevant for airway disease. In particular, we determined type I versus type III IFN expression in human epithelial cells and monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). In epithelial cells, HMPV induced only low levels of IFN- mRNA, while a robust mRNA expression of IFN-s was found in epithelial cells, MDMs, and MDDCs. In addition, we determined induction of the interferon regulatory factors (IRFs) IRF1, IRF3, and IRF7 and critical inflammatory cytokines (IL-6, IP-10, and IL-1). Interestingly, IRF1 mRNA was predominantly induced in MDMs and MDDCs. Overall, our results suggest that for HMPV infection of MDDCs, MDMs, NECs, and A549 cells (the cell types examined), cell type is a strong determinator of the ability of HMPV to induce different innate immune mediators. HMPV induces the transcription of IFN- and IRF1 to higher extents in MDMs and MDDCs than in A549s and NECs, whereas the induction of type III IFN- and IRF7 is considerable in MDMs, MDDCs, and A549 epithelial cells.
人偏肺病毒（HMPV）可能导致严重的呼吸道疾病。早期针对 HMPV 等病毒的先天免疫反应的特征是诱导抗病毒干扰素（IFNs）和促炎免疫介质，这些介质对于塑造适应性免疫反应至关重要。尽管已经在小鼠和鼠免疫细胞中对 HMPV 的先天免疫反应进行了全面研究，但在人类细胞中，关于这些反应的信息较少，尤其是在比较相同 HMPV 株感染的不同细胞类型时。本研究的目的是描述与人呼吸道疾病相关的人原代细胞中关键先天免疫介质对 HMPV 的诱导 mRNA 表达。特别是，我们确定了人上皮细胞和单核细胞衍生的巨噬细胞（MDMs）和树突状细胞（MDDCs）中 I 型和 III 型 IFN 的表达。在上皮细胞中，HMPV 仅诱导低水平的 IFN-β mRNA，而在上皮细胞、MDMs 和 MDDCs 中发现了 IFN-λ的强烈 mRNA 表达。此外，我们还确定了干扰素调节因子（IRFs）IRF1、IRF3 和 IRF7 和关键炎症细胞因子（IL-6、IP-10 和 IL-1）的诱导。有趣的是，IRF1 mRNA 主要在上皮细胞中诱导。总体而言，我们的结果表明，对于 HMPV 感染 MDDCs、MDMs、NECs 和 A549 细胞（检查的细胞类型），细胞类型是 HMPV 诱导不同先天免疫介质的能力的一个重要决定因素。与 A549 细胞和 NECs 相比，HMPV 在 MDMs 和 MDDCs 中诱导 IFN-和 IRF1 的转录水平更高，而在 MDMs、MDDCs 和 A549 上皮细胞中诱导 III 型 IFN-和 IRF7 的水平相当高。
