英国伦敦帝国理工学院Peter J. M. Openshaw、Christopher Chiu和Cecilia Johansson研究组合作取得一项新突破。他们发现呼吸道粘膜中性粒细胞炎症易诱发呼吸道合胞病毒（RSV）感染。相关论文发表在2020年10月9日出版的《科学》杂志上。

他们对58名志愿者进行了RSV治疗，其中57％被感染。接触前的粘膜中性粒细胞活化高度预示了有症状的RSV疾病。这与粘膜白细胞介素17A（IL-17A）和其他介质的症状前快速下降有关。相反，能抵抗感染的患者表现出症状前的IL-17和肿瘤坏死因子相关途径的激活。感染的脆弱性与基线微生物组无关，但在小鼠中是通过感染前趋化因子驱动的嗜中性粒细胞途径募集，然后在小鼠中再生，这导致由肺CD8 + T细胞浸润介导的疾病增强。

因此，RSV暴露时的粘膜嗜中性炎症增强了敏感性，在症状发作之前揭示了动态的、时间依赖性的局部免疫反应，并解释了接触病原体后迄今无法预测的结果。

据介绍，病毒接触的可变结果仅由已知因素部分解释。

附：英文原文

Title: Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Author: Maximillian S. Habibi, Ryan S. Thwaites, Meiping Chang, Agnieszka Jozwik, Allan Paras, Freja Kirsebom, Augusto Varese, Amber Owen, Leah Cuthbertson, Phillip James, Tanushree Tunstall, David Nickle, Trevor T. Hansel, Miriam F. Moffatt, Cecilia Johansson, Christopher Chiu, Peter J. M. Openshaw

Issue&Volume: 2020/10/09

Abstract: The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.

DOI: 10.1126/science.aba9301

Source: https://science.sciencemag.org/content/370/6513/eaba9301