TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis.
TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis.
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DOI：
10.1016/j.cellimm.2009.03.008
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发表时间：
2009
影响因子：
4.3
通讯作者：
Harding, Clifford V.
中科院分区：
文献类型：
--
作者：
Drage, Michael G.;Pecora, Nicole D.;Hise, Amy G.;Febbraio, Maria;Silverstein, Roy L.;Golenbock, Douglas T.;Boom, W. Henry;Harding, Clifford V.
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）通过Toll样受体2（Toll like receptor 2，TLR 2）信号传导调节抗原呈递细胞（antigen presenting cell，APC）。Mtb脂蛋白，包括LpqH、LprA、LprG和PhoS 1，是TLR 2激动剂，但它们的共受体需求是未知的。我们研究了Mtb脂蛋白在TLR 2 −/−、TLR 1 −/−、TLR 6 −/−、CD 14 −/−和CD 36 −/−巨噬细胞中诱导的反应。对LprA、LprG、LpqH和PhoS 1的反应完全依赖于TLR 2。LprG、LpqH和PhoS 1依赖于TLR 1，但LprA不需要TLR 1。没有一种脂蛋白需要TLR 6，尽管不能排除TLR 6的冗余贡献。CD 14有助于检测LprA、LprG和LpqH，而CD 36仅有助于检测LprA。肺APC亚群的研究显示，CD 11bhigh/CD 11 clow肺巨噬细胞的TLR 2表达低于CD 11blow/CD 11 chigh肺泡巨噬细胞，这与肺巨噬细胞对LpqH的低反应性相关。因此，肺APC亚群在TLR表达方面不同，这可能决定对Mtb的应答差异。
Mycobacterium tuberculosis (Mtb) signals through Toll-like receptor 2 (TLR2) to regulate antigen presenting cells (APCs). Mtb lipoproteins, including LpqH, LprA, LprG and PhoS1, are TLR2 agonists, but their co-receptor requirements are unknown. We studied Mtb lipoprotein-induced responses in TLR2−/−, TLR1−/−, TLR6−/−, CD14−/− and CD36−/− macrophages. Responses to LprA, LprG, LpqH and PhoS1 were completely dependent on TLR2. LprG, LpqH, and PhoS1 were dependent on TLR1, but LprA did not require TLR1. None of the lipoproteins required TLR6, although a redundant contribution by TLR6 cannot be excluded. CD14 contributed to detection of LprA, LprG and LpqH, whereas CD36 contributed only to detection of LprA. Studies of lung APC subsets revealed lower TLR2 expression by CD11bhigh/CD11clow lung macrophages than CD11blow/CD11chigh alveolar macrophages, which correlated with hyporesponsiveness of lung macrophages to LpqH. Thus, lung APC subsets differ in TLR expression, which may determine differences in responses to Mtb.
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影响因子：
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作者：
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