Ex vivo and in vivo evidence that cigarette smoke-exposed T regulatory cells impair host immunity against Mycobacterium tuberculosis.
Ex vivo and in vivo evidence that cigarette smoke-exposed T regulatory cells impair host immunity against Mycobacterium tuberculosis.
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DOI：
10.3389/fcimb.2023.1216492
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发表时间：
2023
影响因子：
5.7
通讯作者：
Chan, Edward D.
中科院分区：
文献类型：
--
作者：
Bai, Xiyuan;Verma, Deepshikha;Garcia, Cindy;Musheyev, Ariel;Kim, Kevin;Fornis, Lorelenn;Griffith, David E.;Li, Li;Whittel, Nicholas;Gadwa, Jacob;Ohanjanyan, Tamara;Eggleston, Matthew J.;Galvan, Manuel;Freed, Brian M.;Ordway, Diane;Chan, Edward D.
吸烟（CS）暴露与结核病（TB）易感性之间存在强烈的流行病学联系。巨噬细胞和小鼠研究表明，CS和尼古丁损害宿主保护性免疫细胞对结核分枝杆菌（MTB）感染。虽然CS和尼古丁可以激活调节性T细胞（T细胞），但关于CS如何影响MTB感染的这些免疫抑制细胞知之甚少。我们研究了CS暴露的TdR是否会加剧与人巨噬细胞共培养的MTB感染，以及在接受来自供体CS暴露小鼠的TdR过继转移的受体小鼠中。我们发现，暴露于CS提取物的原代人THP通过抑制吞噬体-溶酶体融合和自噬体形成而损害未暴露的人巨噬细胞控制MTB感染的能力。在暴露于CS提取物的T细胞上中和CTLA-4消除了巨噬细胞和Treg共培养物中MTB感染的受损控制。在内源性Tcl 3耗竭的Foxp 3 +GFP+DTR+（Thy1.2）小鼠中，从供体CS暴露的B6.PL（Thy1.1）小鼠过继转移Tcl 3，随后MTB感染Thy1.2小鼠，导致肺和脾中MTB的负荷大于从空气暴露小鼠接受Tcl 3的小鼠。接受来自供体CS暴露小鼠的TCL 4并感染MTB的小鼠在肺中具有适度但显著减少的白细胞介素-12阳性树突状细胞和干扰素-γ阳性CD 4 + T细胞的数量，并且在肺和脾中具有增加的总程序性细胞死亡蛋白-1（PD-1）阳性CD 4 + T细胞的数量。以前的研究表明，CS损害巨噬细胞和宿主保护性T效应细胞在控制MTB感染。我们现在表明，CS暴露的THBE也可以损害与巨噬细胞共培养和鼠模型中MTB的控制。
A strong epidemiologic link exists between cigarette smoke (CS) exposure and susceptibility to tuberculosis (TB). Macrophage and murine studies showed that CS and nicotine impair host-protective immune cells against Mycobacterium tuberculosis (MTB) infection. While CS and nicotine may activate T regulatory cells (Tregs), little is known about how CS may affect these immunosuppressive cells with MTB infection. We investigated whether CS-exposed Tregs could exacerbate MTB infection in co-culture with human macrophages and in recipient mice that underwent adoptive transfer of Tregs from donor CS-exposed mice. We found that exposure of primary human Tregs to CS extract impaired the ability of unexposed human macrophages to control an MTB infection by inhibiting phagosome-lysosome fusion and autophagosome formation. Neutralizing CTLA-4 on the CS extract-exposed Tregs abrogated the impaired control of MTB infection in the macrophage and Treg co-cultures. In Foxp3+GFP+DTR+ (Thy1.2) mice depleted of endogenous Tregs, adoptive transfer of Tregs from donor CS-exposed B6.PL(Thy1.1) mice with subsequent MTB infection of the Thy1.2 mice resulted in a greater burden of MTB in the lungs and spleens than those that received Tregs from air-exposed mice. Mice that received Tregs from donor CS-exposed mice and infected with MTB had modest but significantly reduced numbers of interleukin-12-positive dendritic cells and interferon-gamma-positive CD4+ T cells in the lungs, and an increased number of total programmed cell death protein-1 (PD-1) positive CD4+ T cells in both the lungs and spleens. Previous studies demonstrated that CS impairs macrophages and host-protective T effector cells in controlling MTB infection. We now show that CS-exposed Tregs can also impair control of MTB in co-culture with macrophages and in a murine model.
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在传染病和疫苗接种中，人类宿主与病原体之间的界面的调节性T细胞。
影响因子：
7.3
作者：
Boer MC;Joosten SA;Ottenhoff TH
通讯作者：
Ottenhoff TH
影响因子：
7.3
作者：
Bai, Xiyuan;Bai, An;Chan, Edward D.
通讯作者：
Chan, Edward D.
影响因子：
24.3
作者：
Isajevs, S.;Taivans, I.;Kratovska, A.
通讯作者：
Kratovska, A.
DOI：
10.1007/978-1-4614-6111-1_9
发表时间：
2013-01-01
期刊：
NEW PARADIGM OF IMMUNITY TO TUBERCULOSIS
影响因子：
--
作者：
Larson, Ryan P.;Shafiani, Shahin;Urdahl, Kevin B.
通讯作者：
Urdahl, Kevin B.
影响因子：
--
作者：
Ko JH;Yoon SO;Lee HJ;Oh JY
通讯作者：
Oh JY