Intestinal Microbiota Disruption Reduces Regulatory T Cells and Increases Respiratory Viral Infection Mortality Through Increased IFNγ Production.
Intestinal Microbiota Disruption Reduces Regulatory T Cells and Increases Respiratory Viral Infection Mortality Through Increased IFNγ Production.
复制标题
DOI：
10.3389/fimmu.2018.01587
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Salzman NH
中科院分区：
文献类型：
--
作者：
Grayson MH;Camarda LE;Hussain SA;Zemple SJ;Hayward M;Lam V;Hunter DA;Santoro JL;Rohlfing M;Cheung DS;Salzman NH
胃肠道微生物群的改变间接调节特应性疾病的风险，但对呼吸道病毒感染的影响尚不清楚。利用小鼠1型副粘病毒仙台病毒（SeV），我们研究了改变胃肠道微生物群对肺部抗病毒免疫反应的影响。C57BL6小鼠在感染SeV前或感染期间用链霉素治疗，观察其免疫应答。摄入不可吸收的抗生素链霉素导致肠道微生物多样性显著减少，但对肺部微生物群没有显著影响。胃肠道多样性减少后，呼吸道病毒感染的死亡率大大增加（p < 0.0001）。死亡率的增加与免疫反应失调有关，其特征是肺（p = 0.01）和肠（p = 0.03）调节性T细胞（Tregs）减少，肺IFNγ (p = 0.049)、IL-6 （p = 0.015）和CCL2 （p = 0.037）增加。Treg细胞过继转移或中和IFNγ可防止死亡率增加。此外，Lin−CD4+细胞似乎是IFNγ增加的潜在来源。总之，这些结果表明，胃肠道微生物群调节远处粘膜部位的免疫反应，并有能力显著影响呼吸道病毒感染后的死亡率。
Alterations in gastrointestinal microbiota indirectly modulate the risk of atopic disease, but effects on respiratory viral infections are less clear. Using the murine paramyxoviral virus type 1, Sendai virus (SeV), we examined the effect of altering gastrointestinal microbiota on the pulmonary antiviral immune response. C57BL6 mice were treated with streptomycin before or during infection with SeV and resulting immune response studied. Ingestion of the non-absorbable antibiotic streptomycin led to a marked reduction in intestinal microbial diversity without a significant effect on lung microbiota. Reduction in diversity in the gastrointestinal tract was followed by greatly increased mortality to respiratory viral infection (p < 0.0001). This increase in mortality was associated with a dysregulated immune response characterized by decreased lung (p = 0.01) and intestinal (p = 0.03) regulatory T cells (Tregs), and increased lung IFNγ (p = 0.049), IL-6 (p = 0.015), and CCL2 (p = 0.037). Adoptive transfer of Treg cells or neutralization of IFNγ prevented increased mortality. Furthermore, Lin−CD4+ cells appeared to be a potential source of the increased IFNγ. Together, these results demonstrate gastrointestinal microbiota modulate immune responses at distant mucosal sites and have the ability to significantly impact mortality in response to a respiratory viral infection.
登录
查看更多内容
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Biagi E;Nylund L;Candela M;Ostan R;Bucci L;Pini E;Nikkïla J;Monti D;Satokari R;Franceschi C;Brigidi P;De Vos W
通讯作者：
De Vos W
影响因子：
6.4
作者：
BOHNHOFF, M;MILLER, CP
通讯作者：
MILLER, CP
DOI：
10.4049/jimmunol.1002456
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheung DS;Ehlenbach SJ;Kitchens RT;Riley DA;Thomas LL;Holtzman MJ;Grayson MH
通讯作者：
Grayson MH
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K