Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.
Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.
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DOI：
10.1126/science.aba9301
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发表时间：
2020-10-09
期刊：
影响因子：
--
通讯作者：
Openshaw PJM
中科院分区：
文献类型：
--
作者：
Habibi MS;Thwaites RS;Chang M;Jozwik A;Paras A;Kirsebom F;Varese A;Owen A;Cuthbertson L;James P;Tunstall T;Nickle D;Hansel TT;Moffatt MF;Johansson C;Chiu C;Openshaw PJM
病毒暴露的可变结果仅部分由已知因素解释。我们给58名志愿者注射呼吸道合胞病毒（RSV），其中57%被感染。暴露前粘液性中性粒细胞活化高度预测有症状的RSV疾病。这与症状前粘膜白细胞介素-17A（IL-17 A）和其他介质的快速下降有关。相反，那些抵抗感染的人表现出IL-17和肿瘤坏死因子相关途径的症状前激活。对感染的易感性与基线微生物组无关，但在小鼠中通过感染前趋化因子驱动的中性粒细胞气道募集而再现，这导致肺部CD 8 + T细胞浸润介导的疾病增强。因此，RSV暴露时的粘膜嗜酸性炎症增强了易感性，揭示了症状发作前动态的、时间依赖性的局部免疫应答，并解释了病原体暴露的迄今不可预测的结果。
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.
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影响因子：
6.4
作者：
Bagga, Bindiya;Cehelsky, Jeffrey E.;DeVincenzo, John P.
通讯作者：
DeVincenzo, John P.
影响因子：
4
作者：
Huang, Huaqiong;Saravia, Jordy;You, Dahui;Shaw, Aaron J.;Cormier, Stephania A.
通讯作者：
Cormier, Stephania A.
DOI：
10.1084/jem.20140825
发表时间：
2015-05-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goritzka M;Makris S;Kausar F;Durant LR;Pereira C;Kumagai Y;Culley FJ;Mack M;Akira S;Johansson C
通讯作者：
Johansson C
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
5.4
作者：
Goritzka M;Durant LR;Pereira C;Salek-Ardakani S;Openshaw PJ;Johansson C
通讯作者：
Johansson C