Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
复制标题
DOI：
10.1371/journal.ppat.1004080
复制
发表时间：
2014-06
期刊：
影响因子：
6.7
通讯作者：
Loke P
中科院分区：
文献类型：
--
作者：
Girgis NM;Gundra UM;Ward LN;Cabrera M;Frevert U;Loke P
在慢性辅助性T细胞2炎性病症期间积聚的替代活化巨噬细胞（AAM）可通过驻留巨噬细胞的增殖或单核细胞衍生细胞的募集而产生。曼氏血吸虫虫卵周围形成的肝肉芽肿需要AAM来限制组织损伤。在这里，我们的特点是单核细胞和巨噬细胞的动态感染CX3CR1GFP/+小鼠的肝脏。CX3CR1-GFP+单核细胞和巨噬细胞在感染期间聚集在卵周围和肉芽肿中，并上调PD-L2表达，表明分化为AAM。CX3CR1-GFP + Ly6Clow单核细胞的活体成像揭示了巡逻行为的改变，包括在未被肉芽肿包裹的卵周围的停滞。血液和组织中CX3CR1-GFP+细胞的差异标记显示，组织中PD-L2 + CX3CR1-GFP + AAM的CD4 + T细胞依赖性积累为肉芽肿形成。通过将Ly6Chigh和Ly6Clow单核细胞过继转移到感染小鼠中，我们发现AAM主要来源于转移的Ly6Chigh单核细胞，但这些细胞可能会转变为Ly6Clow状态并在血管系统中采取巡逻行为。因此，在慢性蠕虫感染期间，AAM可以经由CD4 + T细胞的帮助从募集的Ly6Chigh单核细胞产生。巨噬细胞将根据不同类型的炎症反应采用不同的特征。在寄生蠕虫如曼氏血吸虫感染期间，巨噬细胞采用“交替激活”或M2表型（AAM）。这些AAM对于保护肝细胞免受寄生虫卵引起的损伤是重要的。在这里，我们研究了感染S的小鼠肝脏中AAM的细胞来源。mansoni我们发现AAM在S. mansoni感染来自单核细胞而不是来自组织驻留的巨噬细胞。单核细胞可以分离成Ly6C高和Ly6C低单核细胞亚群。我们证明，这是Ly6Chigh单核细胞的前体AAM在肝肉芽肿，但他们可能采取的行为Ly6Clow单核细胞对虫卵。此外，这些Ly6C高单核细胞需要CD4 + T细胞的帮助，以分化成AAM或维持这种表型。
Alternatively activated macrophages (AAM) that accumulate during chronic T helper 2 inflammatory conditions may arise through proliferation of resident macrophages or recruitment of monocyte-derived cells. Liver granulomas that form around eggs of the helminth parasite Schistosoma mansoni require AAM to limit tissue damage. Here, we characterized monocyte and macrophage dynamics in the livers of infected CX3CR1GFP/+ mice. CX3CR1-GFP+ monocytes and macrophages accumulated around eggs and in granulomas during infection and upregulated PD-L2 expression, indicating differentiation into AAM. Intravital imaging of CX3CR1-GFP+ Ly6Clow monocytes revealed alterations in patrolling behavior including arrest around eggs that were not encased in granulomas. Differential labeling of CX3CR1-GFP+ cells in the blood and the tissue showed CD4+ T cell dependent accumulation of PD-L2+ CX3CR1-GFP+ AAM in the tissues as granulomas form. By adoptive transfer of Ly6Chigh and Ly6Clow monocytes into infected mice, we found that AAM originate primarily from transferred Ly6Chigh monocytes, but that these cells may transition through a Ly6Clow state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited Ly6Chigh monocytes via help from CD4+ T cells. Macrophages will adopt different characteristics based on different types of inflammatory responses. During infection by parasitic helminths such as Schistosoma mansoni, macrophages adopt an “alternatively activated” or M2 phenotype (AAM). These AAM are important for protecting liver hepatocytes from damage caused by the parasite eggs. Here, we examine the cellular source of AAM in the liver of mice infected with S. mansoni. We find that AAM during S. mansoni infection come from monocytes and not from tissue resident macrophages. Monocytes can be separated into Ly6Chigh and Ly6Clow monocyte subsets. We demonstrate that it is the Ly6Chigh monocytes that are the precursors of AAM in the liver granulomas, but they might adopt the behavior of Ly6Clow monocytes in response to schistosome eggs. Additionally, these Ly6CHigh monocytes require help from CD4+ T cells in order to differentiate into AAM or to maintain this phenotype.
登录
查看更多内容
影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
通讯作者：
Chawla, Ajay
DOI：
10.1084/jem.20130761
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Obata-Ninomiya K;Ishiwata K;Tsutsui H;Nei Y;Yoshikawa S;Kawano Y;Minegishi Y;Ohta N;Watanabe N;Kanuka H;Karasuyama H
通讯作者：
Karasuyama H
影响因子：
6.7
作者：
Broadhurst MJ;Leung JM;Lim KC;Girgis NM;Gundra UM;Fallon PG;Premenko-Lanier M;McKerrow JH;McCune JM;Loke P
通讯作者：
Loke P
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.