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细胞外基质蛋白在实验性副球孢子菌病病程中的作用

Involvement of extracellular matrix proteins in the course of experimental paracoccidioidomycosis.

作者信息

González Angel, Gómez Beatriz L, Muñoz Cesar, Aristizabal Beatriz H, Restrepo Angela, Hamilton Andrew J, Cano Luz E

机构信息

Medical and Experimental Mycology Group, Corporación para Investigaciones Biológicas, Medellín, Colombia.

出版信息

FEMS Immunol Med Microbiol. 2008 Jun;53(1):114-25. doi: 10.1111/j.1574-695X.2008.00411.x. Epub 2008 Apr 9.

Abstract

We aimed at determining involvement of extracellular matrix proteins (ECMp) and an ECM-binding adhesin (32-kDa protein) from Paracoccidioides brasiliensis, in the course of experimental paracoccidioidomycosis. BALB/c mice were infected with P. brasiliensis conidia previously incubated with soluble laminin, fibronectin and fibrinogen or a mAb against the fungal adhesin. Inflammatory response, chitin levels and cytokine production at different postinfection periods were determined. Chitin was significantly decreased in lungs of mice infected with ECMp-treated conidia when compared with controls at week 8, especially with laminin and fibrinogen. Contrariwise, when animals were infected with mAb-treated conidia no differences in chitin content were found. The observed inflammatory reaction in lungs was equivalent in all cases. IFN-gamma increased significantly in lungs from mice infected with soluble ECMp - (at day 4 and week 12) or mAb-treated conidia (at week 12) when compared with animals infected with untreated conidia. Significant increased levels of tumour necrosis factor-alpha were observed at 8 weeks in animals infected with ECMp-treated conidia while no differences were observed during the remaining periods. These findings point toward an inhibitory effect of ECMp on P. brasiliensis conidia infectivity and suggest that these proteins may interfere with conidia initial adhesion to host tissues probably modulating the immune response in paracoccidioidomycosis.

摘要

我们旨在确定巴西副球孢子菌的细胞外基质蛋白(ECMp)和一种ECM结合黏附素(32 kDa蛋白)在实验性副球孢子菌病过程中的作用。将BALB/c小鼠感染预先与可溶性层粘连蛋白、纤连蛋白和纤维蛋白原或抗真菌黏附素的单克隆抗体孵育过的巴西副球孢子菌分生孢子。测定不同感染后时期的炎症反应、几丁质水平和细胞因子产生情况。与对照组相比,在第8周时,感染经ECMp处理的分生孢子的小鼠肺部几丁质显著减少,尤其是与层粘连蛋白和纤维蛋白原孵育的情况。相反,当动物感染经单克隆抗体处理的分生孢子时,未发现几丁质含量有差异。在所有情况下,观察到的肺部炎症反应相当。与感染未处理分生孢子的动物相比,感染可溶性ECMp处理的分生孢子(第4天和第12周)或单克隆抗体处理的分生孢子(第12周)的小鼠肺部IFN-γ显著增加。在感染经ECMp处理的分生孢子的动物中,在第8周时观察到肿瘤坏死因子-α水平显著升高,而在其余时期未观察到差异。这些发现表明ECMp对巴西副球孢子菌分生孢子的感染性有抑制作用,并表明这些蛋白质可能干扰分生孢子与宿主组织的初始黏附,可能在副球孢子菌病中调节免疫反应。

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