Roles of Toll-like receptor 2 (TLR2) and superantigens on adaptive immune responses during CNS staphylococcal infection.

Roles of Toll-like receptor 2 (TLR2) and superantigens on adaptive immune responses during CNS staphylococcal infection.
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DOI:
10.1016/j.bbi.2010.09.016
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发表时间:
2011-07
影响因子:
15.1
通讯作者:
Kielian, Tammy
Kielian, Tammy
中科院分区:
医学1区
文献类型:
--
作者:
Vidlak, Debbie;Mariani, Monica M.;Aldrich, Amy;Liu, Shuliang;Kielian, Tammy

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金黄色葡萄球菌是脑脓肿的常见病原体,具有多种操纵宿主免疫的毒力因子。一个例子是超抗原(SAG),其克隆扩增携带特异性Vβ受体的T细胞亚群。Toll样受体2(TLR 2)是与S. aureus识别。然而,TLR 2,SAG和适应性免疫在脑脓肿形成过程中的相互作用尚未被研究,并可能揭示宿主-病原体相互作用调节保护性免疫的新见解。在用S.金黄色葡萄球菌临床分离株。与WT群体相比,TLR 2 KO小鼠的脑水肿中自然杀伤T(NKT)和γδ T细胞浸润均增加,并产生更多的IL-17和IFN-γ,这可能是由于在这些动物中观察到的细菌负荷升高所致。对SAG反应性T细胞的分析显示,主要的Vβ 8.1,8.2浸润与葡萄球菌肠毒素B(SE B)反应,而SEA反应性Vβ11 T细胞数量较少。与WT动物相比,TLR 2 KO小鼠的脑肿瘤具有较少的Vβ 8.1、8.2和Vβ11 T细胞,并且产生较少的TNF-α和IFN-γ。用纯化的SEB处理原代小胶质细胞增加了对TLR 2配体Pam 3Cys应答的TNF-α产生,这可能有助于放大CNS S期间的促炎级联反应。金黄色葡萄球菌感染。总的来说,这些研究表明TLR 2影响对S的适应性免疫。金黄色葡萄球菌感染和调节SAG反应。
Staphylococcus aureus is a common etiologic agent of brain abscesses and possesses numerous virulence factors that manipulate host immunity. One example is superantigens (SAG) that clonally expand T cell subsets bearing specific Vβ receptors. Toll-like receptor 2 (TLR2) is one receptor implicated in S. aureus recognition. However, the interplay between TLR2, SAG, and adaptive immunity during brain abscess formation has not yet been investigated and could reveal novel insights into host-pathogen interactions for regulating protective immunity. A comprehensive analysis of abscess-associated T cell populations in TLR2 KO and WT mice was performed following infection with a S. aureus clinical isolate. Both natural killer T (NKT) and γδ T cell infiltrates were increased in brain abscesses of TLR2 KO mice and produced more IL-17 and IFN-γ compared to WT populations, which could have resulted from elevated bacterial burdens observed in these animals. Analysis of SAG-reactive T cells revealed a predominant Vβ8.1,8.2 infiltrate reactive with staphylococcal enterotoxin B (SEB), whereas SEA-reactive Vβ11 T cells were less numerous. Brain abscesses of TLR2 KO mice had fewer Vβ8.1,8.2 and Vβ11 T cells and produced less TNF-α and IFN-γ compared to WT animals. Treatment of primary microglia with purified SEB augmented TNF-α production in response to the TLR2 ligand Pam3Cys, which may serve to amplify proinflammatory cascades during CNS S. aureus infection. Collectively, these studies demonstrate that TLR2 impacts adaptive immunity to S. aureus infection and modulates SAG responses.
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发表时间: 2010-03-26
期刊: Immunity
影响因子: 32.4
作者:
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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发表时间: 2004-06-01
影响因子: 3.3
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发表时间: 2004-02-01
影响因子: 4.7
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影响因子: 5.7
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