Balloy Viviane, Si-Tahar Mustapha, Takeuchi Osamu, Philippe Bruno, Nahori Marie-Anne, Tanguy Myriam, Huerre Michel, Akira Shizuo, Latgé Jean-Paul, Chignard Michel
Unité de Défense Innée et Inflammation, Inserm E336, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France.
Infect Immun. 2005 Sep;73(9):5420-5. doi: 10.1128/IAI.73.9.5420-5425.2005.
Aspergillus fumigatus, an opportunistic fungal pathogen, causes severe and usually fatal invasive pulmonary aspergillosis in immunocompromised hosts. Interestingly, Drosophila cells lacking the Toll protein are prone to A. fumigatus infection. In the current study, we looked for the involvement of Toll-like receptor 2 (TLR2) in the recognition of A. fumigatus by analyzing the in vivo and ex vivo responses of immunocompromised TLR2(-/-) and TLR2(+/+) mice to this fungus. Upon intratracheal administration of conidia, survival and tumor necrosis factor alpha (TNF-alpha), interleukin-12, and macrophage inhibitory protein-2 alpha concentrations in the airspaces of TLR2(-/-) mice were significantly lower than those of TLR2(+/+) animals. In vitro analysis of TNF-alpha production by conidia-challenged alveolar macrophages from TLR2(-/-) revealed a significant deficiency in comparison with macrophages from TLR2(+/+) mice. Infected TLR2(-/-) mice also have a higher respiratory distress and a higher pathogen burden than TLR2(+/+) mice. These data demonstrate that TLR2 plays a significant role in the defense of the host against A. fumigatus infection.
烟曲霉是一种机会性真菌病原体，可在免疫功能低下的宿主中引起严重且通常致命的侵袭性肺曲霉病。有趣的是，缺乏Toll蛋白的果蝇细胞易于受到烟曲霉的感染。在当前的研究中，我们通过分析免疫功能低下的TLR2(-/-)和TLR2(+/+)小鼠对这种真菌的体内和体外反应，来探寻Toll样受体2（TLR2）在识别烟曲霉中的作用。经气管内给予分生孢子后，TLR2(-/-)小鼠气腔内的存活率、肿瘤坏死因子α（TNF-α）、白细胞介素-12和巨噬细胞抑制蛋白-2α浓度均显著低于TLR2(+/+)动物。对来自TLR2(-/-)的经分生孢子刺激的肺泡巨噬细胞产生TNF-α的体外分析显示，与来自TLR2(+/+)小鼠的巨噬细胞相比存在显著缺陷。受感染的TLR2(-/-)小鼠也比TLR2(+/+)小鼠有更高的呼吸窘迫和更高的病原体负荷。这些数据表明，TLR2在宿主抵御烟曲霉感染的防御中发挥着重要作用。
