Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration.
Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration.
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DOI：
10.1038/ncomms1474
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发表时间：
2011-09-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
B族链球菌（GBS）是新生儿脑膜炎的主要病因。细菌细胞表面附属物，称为皮利，最近在链球菌病原体中被描述，包括GBS。菌毛尖端粘附素（PilA）有助于GBS粘附于血脑屏障（BBB）内皮;然而，宿主受体和PilA在中枢神经系统（CNS）疾病发病机制中的作用尚不清楚。在这里，我们表明PilA结合胶原蛋白，其促进GBS与α2β1整联蛋白的相互作用，导致感染期间宿主趋化因子表达和中性粒细胞募集的激活。感染PilA缺陷突变体的小鼠表现出延迟的死亡率，中性粒细胞浸润和细菌CNS传播的减少。我们发现PilA介导的毒力依赖于中性粒细胞的流入，因为中性粒细胞耗竭导致BBB通透性和GBS-BBB渗透性降低。我们的研究结果表明，细菌菌毛，特别是PilA粘附素，具有双重作用，在免疫激活和细菌进入中枢神经系统。B族链球菌可引起新生儿脑膜炎，但细菌如何穿过血脑屏障尚不清楚。在此，细菌皮利粘附分子PilA显示与胶原蛋白结合并促进细菌与在血脑内皮上表达的整联蛋白结合。
Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the α2β1 integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS–BBB penetration. Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS. Group B Streptococcus causes meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.
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影响因子：
15.9
作者：
Kline KA;Dodson KW;Caparon MG;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
2.9
作者：
Kaya, M;Palanduz, A;Karadeniz, A
通讯作者：
Karadeniz, A
影响因子：
6.7
作者：
Hilleringmann M;Giusti F;Baudner BC;Masignani V;Covacci A;Rappuoli R;Barocchi MA;Ferlenghi I
通讯作者：
Ferlenghi I
DOI：
10.1073/pnas.0511017103
发表时间：
2006-02-21
影响因子：
11.1
作者：
Barocchi, MA;Rie, J;Henriques-Normark, B
通讯作者：
Henriques-Normark, B
影响因子：
5.7
作者：
Izore, Thierry;Contreras-Martel, Carlos;Dessen, Andrea
通讯作者：
Dessen, Andrea