MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection.
MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection.
复制标题
在肺内感染期间，MAIT细胞促进炎症单核细胞分化为树突状细胞。
DOI：
10.1084/jem.20160637
复制
发表时间：
2016-11-14
期刊：
影响因子：
--
通讯作者：
Cowley SC
中科院分区：
文献类型：
--
作者：
Meierovics AI;Cowley SC
Cowley和Meierovics表明，在图拉氏方济氏菌肺部感染过程中，粘膜相关不变T细胞(MAIT)促进单核细胞分化为单核细胞来源的树突状细胞。黏膜相关不变T细胞(MAIT)是一种独特的先天T细胞亚群，在图拉氏丝虫肺部感染后，活化的CD4+T细胞迅速募集到肺内是必需的。在这里，我们研究了这种效应背后的机制。我们提供的证据表明，MAIT细胞促进依赖CCR2的单核细胞在图拉氏肺吸虫肺部感染后早期分化为单核细胞来源的DC(Mo-DC)。将Mo-DC过继转移到MAIT细胞缺陷小鼠(mr1CD_4~+T细胞)，挽救了它们在将活化的−/−~+T细胞募集到肺中的缺陷。我们进一步证明，依赖MAIT细胞的GM-CSF的产生在体外促进了单核细胞的分化，而在体内，MR1−/−小鼠肺中GM-CSF的产生被延迟。最后，GM-csf缺陷小鼠在单核细胞分化为Mo-DC方面表现出缺陷，这与mr1−/−小鼠的表型相似。总体而言，我们的数据表明，MAIT细胞促进早期肺GM-CSF的产生，从而驱动炎性单核细胞分化为Mo-DC。此外，mr1−/−小鼠体内Mo-DC的延迟分化是导致活化的CD4+T细胞延迟向肺部募集的原因。这些发现建立了一种新的机制，通过这种机制，MAIT细胞可以促进先天和获得性免疫反应。
Cowley and Meierovics show that mucosa-associated invariant T (MAIT) cells promote the differentiation of monocytes into monocyte-derived dendritic cells during Francisella tularensis LVS pulmonary infection. Mucosa-associated invariant T (MAIT) cells are a unique innate T cell subset that is necessary for rapid recruitment of activated CD4+ T cells to the lungs after pulmonary F. tularensis LVS infection. Here, we investigated the mechanisms behind this effect. We provide evidence to show that MAIT cells promote early differentiation of CCR2-dependent monocytes into monocyte-derived DCs (Mo-DCs) in the lungs after F. tularensis LVS pulmonary infection. Adoptive transfer of Mo-DCs to MAIT cell–deficient mice (MR1−/− mice) rescued their defect in the recruitment of activated CD4+ T cells to the lungs. We further demonstrate that MAIT cell–dependent GM-CSF production stimulated monocyte differentiation in vitro, and that in vivo production of GM-CSF was delayed in the lungs of MR1−/− mice. Finally, GM-CSF–deficient mice exhibited a defect in monocyte differentiation into Mo-DCs that was phenotypically similar to MR1−/− mice. Overall, our data demonstrate that MAIT cells promote early pulmonary GM-CSF production, which drives the differentiation of inflammatory monocytes into Mo-DCs. Further, this delayed differentiation of Mo-DCs in MR1−/− mice was responsible for the delayed recruitment of activated CD4+ T cells to the lungs. These findings establish a novel mechanism by which MAIT cells function to promote both innate and adaptive immune responses.
登录
查看更多内容
影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
Pamer EG
影响因子：
15.9
作者：
Cui, Yue;Franciszkiewicz, Katarzyna;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
32.4
作者：
Croxford, Andrew L.;Lanzinger, Margit;Becher, Burkhard
通讯作者：
Becher, Burkhard
影响因子：
4.4
作者：
Guilliams, Martin;Movahedi, Kiavash;Beschin, Alain
通讯作者：
Beschin, Alain
影响因子：
9.8
作者：
Gold MC;Cerri S;Smyk-Pearson S;Cansler ME;Vogt TM;Delepine J;Winata E;Swarbrick GM;Chua WJ;Yu YY;Lantz O;Cook MS;Null MD;Jacoby DB;Harriff MJ;Lewinsohn DA;Hansen TH;Lewinsohn DM
通讯作者：
Lewinsohn DM