Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile.
Department of Microbiology and Immunology, and Department of Medicine, Albert Einstein College of Medicine , Bronx, NY, USA.
Virulence. 2020 Dec;11(1):580-593. doi: 10.1080/21505594.2020.1770492.
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 CD103DCs 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 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.
人类呼吸道合胞病毒（hRSV）和人类偏肺病毒（hMPV）在全球范围内导致儿童急性呼吸道感染。自然杀伤 T（NKT）细胞是非常规 T 淋巴细胞，其 TCR 识别与 MHC-I 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 感染中的作用。与野生型对照小鼠相比，在 hRSV 感染的 CD1d 缺陷型 BALB/c 小鼠中，肺部浸润的中性粒细胞、嗜酸性粒细胞和 CD103DC 数量减少，IFN-γ产生增加。然而，在感染 hMPV 的 CD1d 缺陷型 BALB/c 组中，未观察到这种效应。重要的是，在 hRSV 感染的小鼠中，CD11b DC 和上皮细胞中的 CD1d 表达减少，但在 hMPV 感染的小鼠中未观察到这种情况。此外，在 hRSV 和 hMPV 感染的小鼠的肺泡巨噬细胞中发现 CD1d 的表达减少。这种 CD1d 表达的减少干扰了 NKT 细胞的激活，进而影响了 IL-2 的分泌，这在针对 hRSV 和 hMPV 的感染实验中得到了证实。此外，在 hRSV 感染的小鼠中，NKT 细胞数量增加，而在 hMPV 感染的小鼠中则没有，导致这些细胞表达 IFN-γ和 IL-2 的减少。总之，hRSV 和 hMPV 可能以不同的方式损害 NKT 细胞的功能，并对这些病毒引发的免疫反应产生影响。
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