ABSTRACT

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) cause acute respiratory tract infections in children worldwide. Natural killer T (NKT) cells are unconventional T lymphocytes, and their TCRs recognize glycolipids bound to the MHC-I-like molecule, CD1d. These cells modulate the inflammatory response in viral infections. Here, we evaluated the contribution of NKT cells in both hRSV and hMPV infections. A significant decrease in the number of neutrophils, eosinophils, and CD103⁺DCs infiltrating to the lungs, as well as an increased production of IFN-γ, were observed upon hRSV-infection in CD1d-deficient BALB/c mice, as compared to wild-type control mice. However, this effect was not observed in the CD1d-deficient BALB/c group, upon infection with hMPV. Importantly, reduced expression of CD1d in CD11b⁺ DCs and epithelial cells was found in hRSV -but not hMPV-infected mice. Besides, a reduction in the expression of CD1d in alveolar macrophages of lungs from hRSV- and hMPV-infected mice was found. Such reduction of CD1d expression interfered with NKT cells activation, and consequently IL-2 secretion, as characterized by in vitro experiments for both hRSV and hMPV infections. Furthermore, increased numbers of NKT cells recruited to the lungs in response to hRSV- but not hMPV-infection was detected, resulting in a reduction in the expression of IFN-γ and IL-2 by these cells. In conclusion, both hRSV and hMPV might be differently impairing NKT cells function and contributing to the immune response triggered by these viruses.

摘要

人呼吸道合胞病毒（hRSV）和人间质肺炎病毒（hMPV）引起全世界儿童的急性呼吸道感染。天然杀伤性T细胞（NKT）是非常规的T淋巴细胞，它们的TCR识别与MHC-1样分子CD1d结合的糖脂。这些细胞调节病毒感染中的炎症反应。在这里，我们评估了NKT细胞在hRSV和hMPV感染中的贡献。中性粒细胞，嗜酸性粒细胞和CD103 ⁺的数量显着减少与野生型对照小鼠相比，在CD1d缺陷的BALB / c小鼠中，hRSV感染后，观察到DC渗透到肺中以及IFN-γ的产生增加。但是，在感染hMPV后，CD1d缺乏的BALB / c组未观察到这种作用。重要的是，在hRSV-感染了hMPV的小鼠中未发现CD11b ⁺ DC和上皮细胞中CD1d的表达降低。此外，发现感染了hRSV和hMPV的小鼠的肺泡巨噬细胞中CD1d的表达降低。CD1d表达的这种降低会干扰NKT细胞的活化，进而干扰IL-2的分泌，这在体外具有特征hRSV和hMPV感染的实验。此外，检测到响应hRSV-感染而非hMPV-感染而募集入肺的NKT细胞数量增加，导致这些细胞的IFN-γ和IL-2表达降低。总之，hRSV和hMPV可能会不同程度地削弱NKT细胞的功能并促进这些病毒触发的免疫反应。