Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection.
Host-derived lipids orchestrate pulmonary γδ T cell response to provide early protection against influenza virus infection.
复制标题
宿主来源的脂质协调肺部 γδT 细胞反应，提供针对流感病毒感染的早期保护
DOI：
10.1038/s41467-021-22242-9
复制
发表时间：
2021-03-26
影响因子：
16.6
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Wang X;Lin X;Zheng Z;Lu B;Wang J;Tan AH;Zhao M;Loh JT;Ng SW;Chen Q;Xiao F;Huang E;Ko KH;Huang Z;Li J;Kok KH;Lu G;Liu X;Lam KP;Liu W;Zhang Y;Yuen KY;Mak TW;Lu L
天然免疫通过引发快速抗病毒应答和桥接适应性免疫对宿主防御是重要的。在这里，我们表明，从病毒感染的宿主细胞释放的内源性脂质激活肺γδ T细胞产生白细胞介素17 A（IL-17 A），以早期保护免受H1N1流感感染。在感染期间，肺γδ T细胞池不断地由胸腺输出补充，新近的迁移者浸润到肺实质和气道中以获得组织驻留特征。单细胞研究鉴定了感染小鼠和肺炎患者中具有TCRγδ hiCD 3 hiAQP 3 hiCXCR 6 hi表型的产生IL-17 A的γδ T（Tγδ17）细胞。从机制上讲，病毒感染期间宿主细胞释放的脂质由肺浸润性CD 1d + B-1a细胞呈递，以通过γδ TCR介导的IRF 4依赖性转录激活γδ T细胞中的IL-17 A产生。在缺乏B-1a细胞或B细胞中CD 1d消除的小鼠中检测到γδ T细胞中IL-17 A产生减少。我们的研究结果确定了一个本地的主机免疫串扰，并定义了重要的细胞和分子介质的早期先天防御肺部病毒感染。甲型流感感染导致γδ T细胞流入和肺中IL-17的产生。在这里，作者表明，这种效应是由受感染细胞释放并由肺部B1 a细胞呈递的CD 1限制性配体引发的。
Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδhiCD3hiAQP3hiCXCR6hi in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d+ B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection. Influenza A infection results in γδ T cell influx and production of IL-17 in the lungs. Here, the authors show that this effect is primed by CD1-restricted ligands that are released by infected cells and presented by B1a cells in the lungs.
登录
查看更多内容
DOI：
10.1084/jem.182.5.1591
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constant S;Pfeiffer C;Woodard A;Pasqualini T;Bottomly K
通讯作者：
Bottomly K
DOI：
10.1038/nri3166
发表时间：
2012-03-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
32.4
作者：
Asmal, M;Colgan, J;Luban, J
通讯作者：
Luban, J
影响因子：
3.8
作者：
Hoq, MM;Suzutani, T;Azuma, M
通讯作者：
Azuma, M
DOI：
10.4049/jimmunol.1000921
发表时间：
2011-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dieudé M;Striegl H;Tyznik AJ;Wang J;Behar SM;Piccirillo CA;Levine JS;Zajonc DM;Rauch J
通讯作者：
Rauch J