Aspergillus fumigatus induces innate immune responses in alveolar macrophages through the MAPK pathway independently of TLR2 and TLR4
Aspergillus fumigatus induces innate immune responses in alveolar macrophages through the MAPK pathway independently of TLR2 and TLR4
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DOI：
10.4049/jimmunol.177.6.3994
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Ibrahim-Granet, Oumaima
中科院分区：
文献类型：
--
作者：
Dubourdeau, Marc;Athman, Rafika;Ibrahim-Granet, Oumaima
烟曲霉菌引起免疫抑制患者侵袭性曲霉病。在免疫活性宿主中，吸入的分生孢子被肺泡巨噬细胞清除。肺泡巨噬细胞参与A.对烟曲霉知之甚少。因此，我们研究了TLR在抗A.以及它们对小鼠肺泡巨噬细胞感染A.烟曲霉分生孢子具体而言，我们研究了MAPK和NF-κ B活化和细胞因子信号传导。我们的研究表明，免疫活性的TLR 2，TLR 4，和MyD 88敲除小鼠并不更容易侵袭性曲霉菌病相比，野生型小鼠和体外磷酸化的MAPK ERK和p38在TLR 2，TLR 4，或MyD 88敲除小鼠与分生孢子刺激后不受影响。体内实验表明ERK是防御A.而NF-κ B B的激活似乎只起次要作用。总之，我们的研究结果表明，TLR 2/4识别和MyD 88信号转导对于A.在免疫活性状态下的烟曲霉菌。此外，我们的数据强调了ERK激活在对A的天然免疫中的重要作用。烟熏。
Aspergillus fumigatus causes invasive aspergillosis in immunosuppressed patients. In the immunocompetent host, inhaled conidia are cleared by alveolar macrophages. The signaling pathways of the alveolar macrophage involved in the clearance of A. fumigatus are poorly understood. Therefore, we investigated the role of TLRs in the immune response against A. fumigatus and their contribution to the signaling events triggered in murine alveolar macrophages upon infection with A. fumigatus conidia. Specifically, we examined the MAPKs and NF-kappa B activation and cytokine signaling. Our investigations revealed that immunocompetent TLR2, TLR4, and MyD88 knockout mice were not more susceptible to invasive aspergillosis as compared with wild-type mice and that the in vitro phosphorylation of the MAPKs ERK and p38 was not affected in TLR2, TLR4, or MyD88 knockout mice following stimulation with conidia. In vivo experiments suggest that ERK was an essential MAPK in the defense against A. fumigatus, whereas the activation of NF-kappa B appeared to play only a secondary role. In conclusion, our findings demonstrate that TLR2/4 recognition and MyD88 signaling are dispensable for the clearance of A. fumigatus under immunocompetent situations. Furthermore, our data stress the important role of ERK activation in innate immunity to A. fumigatus.