Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll-like receptor 2, and phosphatidylinositol-3-kinase

被引:91
作者
Harokopakis, E
Hajishengallis, G
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Ctr Excellence Oral & Craniofacial Biol, New Orleans, LA 70119 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat Dent, New Orleans, LA 70119 USA
[3] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70119 USA
关键词
integrin; toll-like receptor; inflammation monocytes; bacterial fimbriae;
D O I
10.1002/eji.200425883
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD11b-CD18 and other integrins play important roles in immunity and inflammation and require prior activation through inside-out signaling to efficiently bind their ligands. We present evidence for a novel TLR2-dependent signaling pathway that leads to CD11b-CD18 activation in human monocytes or neutrophils upon recognition of Porphyromonas gingivalis fimbriae through CD14. The activated binding-state of CD11b-CD18, which involves induction of conformational changes, was monitored through detection of an activation-specific epitope of CD11b. The ability of fimbriae to induce this activation epitope was significantly inhibited by a mAb to TLR2, but not to TLR4 or unrelated surface molecules. Moreover, the ability of fimbriae to activate CD11b-CD18 was significantly inhibited by pharmacological inhibitors of phosphatidylinositol-3-kinase but not of PKC or of p38 mitogen-activated protein kinase. The signaling pathway activated by fimbriae is distinct from that which is activated by N-formyl-Met-Leu-Phe, a prototypical integrin activator, since the former was insensitive to pertussis toxin. This novel function of TLR2 as a signaling receptor for pathogen-induced activation of CD11b-CD18 may play a significant role in infection-driven chronic inflammatory conditions, such as periodontal disease or atherosclerosis, where P. gingivalis has been implicated.
引用
收藏
页码:1201 / 1210
页数:10
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