Protective role of γδ T cells in cigarette smoke and influenza infection.
Protective role of γδ T cells in cigarette smoke and influenza infection.
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DOI：
10.1038/mi.2017.93
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发表时间：
2018-05
影响因子：
8
通讯作者：
Kheradmand F
中科院分区：
文献类型：
--
作者：
Hong MJ;Gu BH;Madison MC;Landers C;Tung HY;Kim M;Yuan X;You R;Machado AA;Gilbert BE;Soroosh P;Elloso M;Song L;Chen M;Corry DB;Diehl G;Kheradmand F
空气传播的病原体通常会引发患有肺部疾病的吸烟者的严重呼吸衰竭或死亡。吸烟损害了先天免疫对感染的有效性，但吸烟者获得性免疫应答缺陷的潜在机制仍不清楚。我们发现，暴露于慢性香烟烟雾的小鼠从原发性甲型流感肺炎中恢复不佳，I型和II型干扰素（IFN）和病毒特异性免疫球蛋白减少，但主要表达白细胞介素17 A（IL-17 A）的γ δ（γδ）T细胞被招募到肺部。暴露于烟雾并感染甲型流感的IL-17 a-/-小鼠也将γδ T细胞募集到肺部，但与野生型小鼠相反，表达增加的IFN，产生保护性流感特异性抗体，并从感染中恢复。用阻断抗体耗尽IL-17 A显著增加γδ T细胞中的T-bet表达，并改善空气中急性甲型流感感染的恢复，但烟雾暴露小鼠则不然。相比之下，当暴露于烟雾中时，γδ T细胞缺陷小鼠未能对甲型流感产生有效的免疫应答，并显示出死亡率增加。我们的研究结果证明了吸烟者中γδ T细胞的保护作用，并表明烟雾诱导的IL-17 A增加抑制了其最佳抗病毒反应所需的转录程序。
Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited gamma delta (γδ) T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild type mice, expressed increased IFNs, made protective influenza specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses.
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DOI：
10.1164/rccm.201501-0188oc
发表时间：
2015-05-01
影响因子：
24.7
作者：
Hsu, Alan Chen-Yu;Starkey, Malcolm R.;Hansbro, Philip M.
通讯作者：
Hansbro, Philip M.
DOI：
10.1165/rcmb.2009-0254oc
发表时间：
2010-09-01
影响因子：
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作者：
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通讯作者：
Noah, Terry L.
DOI：
10.1126/science.aaa1578
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ciancanelli MJ;Huang SX;Luthra P;Garner H;Itan Y;Volpi S;Lafaille FG;Trouillet C;Schmolke M;Albrecht RA;Israelsson E;Lim HK;Casadio M;Hermesh T;Lorenzo L;Leung LW;Pedergnana V;Boisson B;Okada S;Picard C;Ringuier B;Troussier F;Chaussabel D;Abel L;Pellier I;Notarangelo LD;García-Sastre A;Basler CF;Geissmann F;Zhang SY;Snoeck HW;Casanova JL
通讯作者：
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DOI：
10.4049/jimmunol.0900995
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Crowe CR;Chen K;Pociask DA;Alcorn JF;Krivich C;Enelow RI;Ross TM;Witztum JL;Kolls JK
通讯作者：
Kolls JK
影响因子：
82.9
作者：
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