Histoplasma capsulatum yeast phase-specific protein Yps3p induces Toll-like receptor 2 signaling.
Histoplasma capsulatum yeast phase-specific protein Yps3p induces Toll-like receptor 2 signaling.
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DOI：
10.1186/1742-2094-5-30
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发表时间：
2008-07-07
影响因子：
9.3
通讯作者：
Lokensgard JR
中科院分区：
文献类型：
--
作者：
Aravalli RN;Hu S;Woods JP;Lokensgard JR
在某些地区，组织胞浆菌是真菌感染的常见原因，虽然大多数感染是无症状的，但它能够引起组织胞浆菌病，这是一种播散性的、危及生命的疾病，特别是在免疫功能低下的人中。需要更深入地了解这种宿主-病原体的相互作用，以开发新的治疗策略来对抗致命性感染。尽管有几条证据表明这种真菌对HIV患者具有神经亲和性，但对中枢神经系统组织胞浆感染的免疫生物学知之甚少。本研究的目的是了解在感染初期识别包膜螺旋体的先天神经免疫机制。利用稳定表达小鼠Toll样受体2[TLR2]的293T细胞系，我们发现TLR2识别囊状血吸虫细胞壁蛋白Yps3p并诱导NF-κB的激活。在进一步的实验中，我们测试了Yps3p在原代小胶质细胞中诱导TLR2信号的能力，小胶质细胞是中枢神经系统中驻留的脑巨噬细胞。我们的研究结果表明，Yps3p可以诱导野生型小胶质细胞中的TLR2信号，但不能诱导TLR2 KO小鼠分离的小胶质细胞中的TLR2信号，证实了Yps3p是TLR2的配体。此外，Yps3p诱导的TLR2信号被痘苗病毒编码的TLR抑制剂抑制。这是真菌蛋白作为TLR配体并在初级脑细胞中介导信号传递的第一次展示。
Histoplasma capsulatum is a common cause of fungal infection in certain geographic areas, and although most infections are asymptomatic, it is capable of causing histoplasmosis, a disseminated, life-threatening disease, especially in immunocompromised individuals. A deeper understanding of this host-pathogen interaction is needed to develop novel therapeutic strategies to counter lethal infection. Although several lines of evidence suggest that this fungus is neurotropic in HIV patients, little is known about the immunobiology of Histoplasma infection in the central nervous system [CNS]. The goal of the present study was to understand the innate neuroimmune mechanisms that recognize H. capsulatum during the initial stages of infection. Using a 293T stable cell line expressing murine Toll-like receptor 2 [TLR2], we show here that TLR2 recognizes H. capsulatum cell wall protein Yps3p and induces the activation of NF-κB. In further experiments, we tested the ability of Yps3p to induce signaling from TLR2 in primary microglial cells, the resident brain macrophages of the CNS. Our data show that H. capsulatum Yps3p induced TLR2 signaling in wild-type microglia, but not in microglia isolated from TLR2 KO mice, confirming that Yps3p is a ligand for TLR2. Furthermore, Yps3p-induced TLR2 signaling was suppressed by vaccinia virus-encoded TLR inhibitors. This is the first demonstration of a fungal protein serving as a TLR ligand and mediating signaling in primary brain cells.
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影响因子：
15.3
作者：
Harte, MT;Haga, IR;Maloney, G;Gray, P;Reading, PC;Bartlett, NW;Smith, GL;Bowie, A;O'Neill, LAJ
通讯作者：
O'Neill, LAJ
影响因子：
4.4
作者：
Bellocchio, S;Montagnoli, C;Romani, L
通讯作者：
Romani, L
影响因子：
5.5
作者：
HENDERSON, HM;DEEPE, GS
通讯作者：
DEEPE, GS
影响因子：
8.9
作者：
Klein, CJ;Dinapoli, RP;Meyer, FB
通讯作者：
Meyer, FB
DOI：
10.1007/s100960050368
发表时间：
1999-09-01
影响因子：
4.5
作者：
Knapp, S;Turnherr, M;Rieger, A
通讯作者：
Rieger, A