The RodA hydrophobin on Aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo.
The RodA hydrophobin on Aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo.
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DOI：
10.4049/jimmunol.1300748
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Pearlman E
中科院分区：
文献类型：
--
作者：
Carrion Sde J;Leal SM Jr;Ghannoum MA;Aimanianda V;Latgé JP;Pearlman E
曲霉属和镰刀菌属是世界范围内真菌感染的重要原因。这些丝状真菌的气载孢子（分生孢子）表达赋予疏水性的表面蛋白（疏水蛋白），并且其覆盖否则将诱导宿主免疫细胞应答的细胞壁组分。使用不表达RodA疏水蛋白（ΔrodA）的突变体烟曲霉菌株，以及来自用氢氟酸（HF，其去除A.烟曲霉RodA蛋白），我们观察到曲霉属和镰刀菌分生孢子上的β 1，3-葡聚糖和α-甘露糖的表面暴露增加。我们还发现，ΔrodA和HF处理的分生孢子刺激C57 BL/6小鼠巨噬细胞的NF-κB p65核转位和细胞因子产生显著增加，但对Dectin-1−/−或Dectin-2−/−小鼠则没有。使用A.在C57 BL/6菌株感染烟曲霉角膜后，我们发现ΔrodA分生孢子与亲本G10菌株相比表现出细胞因子产生增加、中性粒细胞浸润以及更快的真菌从C57 BL/6角膜的清除，这依赖于Dectin-1和Dectin-2。总之，这些发现将疏水蛋白RodA鉴定为掩盖分生孢子的Dectin-1和Dectin-2识别的毒力因子，导致中性粒细胞向角膜的募集受损，并增加真菌存活和临床疾病。
Aspergillus and Fusarium species are important causes of fungal infections worldwide. Airborne spores (conidia) of these filamentous fungi express a surface protein that confers hydrophobicity (hydrophobin), and which covers cell wall components that would otherwise induce a host immune cell response. Using a mutant Aspergillus fumigatus strain that does not express the RodA hydrophobin (ΔrodA), and Aspergillus and Fusarium conidia from clinical isolates that were treated with hydrofluoric acid (HF, which removes the A. fumigatus RodA protein), we observed increased surface exposure of β1,3-glucan and α-mannose on Aspergillus and Fusarium conidia. We also found that ΔrodA and HF treated conidia stimulate significantly higher NF-κB p65 nuclear translocation and cytokine production by macrophages from C57BL/6, but not from Dectin-1−/− or Dectin-2−/− mice. Using a murine model of A. fumigatus corneal infection, we found that ΔrodA conidia exhibited increased cytokine production, neutrophil infiltration, and more rapid fungal clearance from C57BL/6 corneas compared with the parent G10 strain, which was dependent on Dectin-1 and Dectin-2. Together, these findings identify the hydrophobin RodA as a virulence factor that masks Dectin-1 and Dectin-2 recognition of conidia, resulting in impaired neutrophil recruitment to the cornea and increased fungal survival and clinical disease.
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DOI：
10.4049/jimmunol.181.1.593
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Tarabishy AB;Aldabagh B;Sun Y;Imamura Y;Mukherjee PK;Lass JH;Ghannoum MA;Pearlman E
通讯作者：
Pearlman E
影响因子：
3.7
作者：
Chamilos G;Ganguly D;Lande R;Gregorio J;Meller S;Goldman WE;Gilliet M;Kontoyiannis DP
通讯作者：
Kontoyiannis DP
影响因子：
3.2
作者：
Oliveira, M.;Ribeiro, H.;Abreu, I.
通讯作者：
Abreu, I.
影响因子：
6.7
作者：
Gringhuis SI;Wevers BA;Kaptein TM;van Capel TM;Theelen B;Boekhout T;de Jong EC;Geijtenbeek TB
通讯作者：
Geijtenbeek TB
影响因子：
32.4
作者：
Saijo, Shinobu;Ikeda, Satoshi;Iwakura, Yoichiro
通讯作者：
Iwakura, Yoichiro