Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis.
Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis.
复制标题
DOI：
10.1016/j.ebiom.2022.103891
复制
发表时间：
2022-03
期刊：
影响因子：
11.1
通讯作者：
de Souza APD
中科院分区：
文献类型：
--
作者：
Antunes KH;Stein RT;Franceschina C;da Silva EF;de Freitas DN;Silveira J;Mocellin M;Leitão L;Fachi JL;Pral LP;Gonzalez A;Oliveira S;Duarte L;Cassão G;Gonçalves JIB;Reis TM;Abbadi BL;Dornelles M;Sperotto NDM;Rigo M;Rodrigues H;Jones M;Epifanio M;Guima S;Setubal JC;Jorge TR;Mansur DS;Mayer FQ;Varela APM;Bizarro CV;Machado P;Basso LA;Polack FP;Custovic A;Vinolo MAR;de Souza APD
肠道微生物群来源的短链脂肪酸（SFCA）乙酸酯通过增加干扰素-β的产生和干扰素刺激基因（ISG）的表达来保护小鼠免受RSV A2菌株感染。然而，SFCA在使用从患者分离的毒株的RSV感染中的作用尚不清楚。我们首先使用从患有RSV细支气管炎住院的婴儿中分离的RSV临床菌株来研究体外SCFA-乙酸盐处理人肺上皮细胞的效果。接下来，我们使用临床分离株检查了SCFA-乙酸酯治疗在RSV感染的小鼠模型中是否有益。我们试图研究肠道微生物群和粪便乙酸盐与RSV细支气管炎住院婴儿疾病严重程度的关系，以及用SCFA-乙酸盐离体治疗其呼吸道上皮细胞是否会影响病毒载量和ISG表达。我们进一步用SCFA-醋酸盐处理来自SARS-CoV-2感染患者的上皮细胞。在体外用SCFA-乙酸盐预处理A549细胞减少了临床分离株的RSV感染，并增加了RIG-I和ISG 15的表达。鼻内给予SCFA醋酸盐治疗的动物恢复得明显更快，RSV临床分离株病毒载量减少，IFNB 1和RIG-I的肺部表达增加。在RIG-I敲除A549细胞中的实验表明，保护依赖于RIG-I的存在。肠道微生物谱与细支气管炎的严重程度和粪便中的醋酸盐相关。SCFA-醋酸盐水平升高与入院时氧饱和度升高和发热持续时间缩短相关。用SCFA-乙酸盐离体处理患者的呼吸道细胞降低了RSV负荷并增加了ISG OAS 1和ISG 15以及病毒识别受体MAVS和RIG-1的表达，但不增加IFNB 1的表达。在SARS-CoV-2感染患者的细胞中未发现这些SCFA醋酸盐效应。SCFA-乙酸盐通过调节RIG-I表达降低RSV感染的严重程度和RSV病毒载量。FAPERGS（FAPERGS/MS/CNPq/SESRS编号03/2017 - PPSUS 17/2551-0001380-8和COVID-19 20/2551-0000258-6）; CNPq 312504/2017-9; CAPES）-财务代码001。
Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-β production and expression of interferon-stimulated genes (ISGs). However, the role of SFCA in RSV infection using strains isolated from patients is unknown. We first used RSV clinical strains isolated from infants hospitalized with RSV bronchiolitis to investigate the effects of in vitro SCFA-acetate treatment of human pulmonary epithelial cells. We next examined whether SCFA-acetate treatment is beneficial in a mouse model of RSV infection using clinical isolates. We sought to investigate the relationship of gut microbiota and fecal acetate with disease severity among infants hospitalized with RSV bronchiolitis, and whether treating their respiratory epithelial cells with SCFA-acetate ex-vivo impacts viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with SCFA-acetate. In vitro pre-treatment of A549 cells with SCFA-acetate reduced RSV infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with SCFA-acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I. Experiments in RIG-I knockout A549 cells demonstrated that the protection relies on RIG-I presence. Gut microbial profile was associated with bronchiolitis severity and with acetate in stool. Increased SCFA-acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients’ respiratory cells with SCFA-acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These SCFA-acetate effects were not found on cells from SARS-CoV-2 infected patients. SCFA-acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6); CNPq 312504/2017-9; CAPES) - Finance Code 001.
登录
查看更多内容
影响因子：
6.7
作者：
Laporte M;Raeymaekers V;Van Berwaer R;Vandeput J;Marchand-Casas I;Thibaut HJ;Van Looveren D;Martens K;Hoffmann M;Maes P;Pöhlmann S;Naesens L;Stevaert A
通讯作者：
Stevaert A
肠蠕虫诱导的I型干扰素信号传导通过与微生物群相互作用来预防肺病毒感染。
DOI：
10.1016/j.jaci.2017.01.016
发表时间：
2017-10
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
McFarlane AJ;McSorley HJ;Davidson DJ;Fitch PM;Errington C;Mackenzie KJ;Gollwitzer ES;Johnston CJC;MacDonald AS;Edwards MR;Harris NL;Marsland BJ;Maizels RM;Schwarze J
通讯作者：
Schwarze J
DOI：
10.1084/jem.20170298
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lynch JP;Werder RB;Loh Z;Sikder MAA;Curren B;Zhang V;Rogers MJ;Lane K;Simpson J;Mazzone SB;Spann K;Hayball J;Diener K;Everard ML;Blyth CC;Forstner C;Dennis PG;Murtaza N;Morrison M;Ó Cuív P;Zhang P;Haque A;Hill GR;Sly PD;Upham JW;Phipps S
通讯作者：
Phipps S
影响因子：
8
作者：
Hasegawa, Kohei;Linnemann, Rachel W.;Camargo, Carlos A., Jr.
通讯作者：
Camargo, Carlos A., Jr.
影响因子：
5.4
作者：
Liu, Ping;Jamaluddin, Mohammad;Brasier, Allan R.
通讯作者：
Brasier, Allan R.