Mannose-capped lipoarabinomannan from Mycobacterium tuberculosis preferentially inhibits sphingosine-1-phosphate-induced migration of Th1 cells.
Mannose-capped lipoarabinomannan from Mycobacterium tuberculosis preferentially inhibits sphingosine-1-phosphate-induced migration of Th1 cells.
复制标题
DOI：
10.4049/jimmunol.1103092
复制
发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Cruikshank WW
中科院分区：
文献类型：
--
作者：
Richmond JM;Lee J;Green DS;Kornfeld H;Cruikshank WW
趋化因子受体的交叉脱敏是调节免疫细胞在炎症部位募集的重要机制。我们曾报道分枝杆菌细胞壁糖磷脂阿拉伯甘露聚糖(ManLAM)能诱导人外周血T细胞趋化。因此，我们研究了ManLAM使T细胞对其他化学诱导剂脱敏的能力，作为分枝杆菌感染期间T细胞归巢功能受损和肺重新募集延迟的潜在机制。我们发现，ManLAM预处理在体外抑制了人或小鼠的幼稚T细胞向淋巴出口信号鞘氨醇-1-磷酸(S1P)的迁移。小鼠气管内给药后，肺引流淋巴结内T细胞，主要是CCR5+(Th1)细胞显著增加。为了研究CCR5的选择性作用，在体外将小鼠T细胞分化为Th1或Th2细胞，并分析了它们在ManLAM处理前后向S1P迁移的能力。Th1细胞的ManLAM预处理抑制了S1P诱导的迁移，但对Th2细胞S1P定向迁移没有影响，提示S1P对这两个亚群的作用不同。PI3K/AKT抑制剂Ly294002抑制Th1细胞S1P定向迁移，ERK抑制剂U0126抑制Th2细胞S1P定向迁移。这些观察表明，S1P诱导的Th1和Th2淋巴细胞的迁移反应是通过不同的信号通路发生的，并进一步表明，在MTB感染期间产生的ManLAM可能起到隔离肺引流淋巴结中的Th1细胞的功能，从而延迟它们向肺的募集。
Chemokine receptor cross-desensitization provides an important mechanism to regulate immune cell recruitment at sites of inflammation. We previously reported that the mycobacterial cell wall glycophospholipid lipoarabinomannan (ManLAM) could induce human peripheral blood T cell chemotaxis. Therefore, we examined the ability of ManLAM to desensitize T cells to other chemoattractants as a potential mechanism for impaired T cell homing and delayed lung recruitment during mycobacterial infection. We found that ManLAM pretreatment inhibited in vitro migration of naïve human or mouse T cells to the lymph node egress signal sphingosine-1-phosphate (S1P). Intratracheal administration of ManLAM in mice resulted in significant increases in T cells, primarily CCR5+ (Th1) cells, in lung draining lymph nodes. To investigate the selective CCR5 effect, mouse T cells were differentiated into Th1 or Th2 populations in vitro and their ability to migrate to S1P with or without ManLAM pretreatment was analyzed. ManLAM pretreatment of Th1 populations inhibited S1P-induced migration, but had no effect on Th2 cell S1P-directed migration suggesting a differential effect by S1P on the two subsets. The PI3K/AKT inhibitor Ly294002 inhibited S1P-directed migration by Th1 cells, whereas the ERK inhibitor U0126 inhibited Th2 cell S1P-directed migration. These observations demonstrate that S1P-induced migratory responses in Th1 and Th2 lymphocytes occurs via different signaling pathways, and suggests further that the production of ManLAM during MTB infection may function to sequester Th1 cells in lung-draining lymph nodes thereby delaying their recruitment to the lung.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
4.5
作者：
Beatty, WL;Rhoades, ER;Russell, DG
通讯作者：
Russell, DG
影响因子：
3.1
作者：
CHAN, J;FAN, X;BLOOM, BR
通讯作者：
BLOOM, BR
影响因子：
3.1
作者：
Chackerian, AA;Alt, JM;Behar, SM
通讯作者：
Behar, SM