Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV + children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV + children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV + children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV + patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV + patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children.

中文翻译：

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改变的自然杀伤细胞免疫表型是临床上严重的儿科 RSV 感染的特征


呼吸道合胞病毒 （RSV） 几乎感染了 2 岁以下的儿童，是儿科住院的主要原因。一部分 RSV 感染儿童 （RSV + 儿童） 出现呼吸衰竭，需要重症监护，但区分严重儿童 RSV 感染的免疫机制尚未完全阐明。自然杀伤 （NK） 细胞是病毒宿主防御的关键先天免疫效应物。在这项对 47 名危重 RSV + 儿童的研究中，我们将 NK 细胞免疫表型和细胞毒功能与临床参数相结合，以确定严重儿科 RSV 疾病的 NK 细胞免疫特征。气道 NK 细胞在气管插管 RSV + 严重低氧血症和机械通气持续时间延长的儿童中增加，并与临床严重程度评分相关。RSV + 患者的外周血 NK 细胞减少，激活受体表达改变，CD69 表达增加，NKG2D 表达降低。来自 RSV + 患者的离体循环 NK 细胞表现出功能障碍，其特征是细胞毒性降低以及异常的免疫突触组装和裂解颗粒运输。NK 细胞频率和表型与定义疾病严重程度的临床指标相关。这些发现表明 NK 细胞在介导 RSV 免疫病理学中的作用，并表明改变的 NK 细胞免疫表型与幼儿的严重 RSV 疾病有关。