Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus.
Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus.
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DOI：
10.4049/jimmunol.0804250
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发表时间：
2009-04-15
期刊：
影响因子：
--
通讯作者：
Steele C
中科院分区：
文献类型：
--
作者：
Werner JL;Metz AE;Horn D;Schoeb TR;Hewitt MM;Schwiebert LM;Faro-Trindade I;Brown GD;Steele C
免疫抑制会增加侵袭性真菌感染的发生率，特别是由机会性霉菌烟曲霉引起的感染。先前的研究表明，Toll 样受体 (TLR) 家族的成员并不是非免疫抑制宿主针对烟曲霉的宿主防御所绝对需要的，这表明其他模式识别受体 (PRR) 也参与其中。我们在此表明，缺乏β-葡聚糖受体Dectin-1 (Dectin-1−/−) 的幼稚小鼠（即未进行药物免疫抑制）对烟曲霉气管内攻击比对照小鼠更敏感，5天内死亡率>80%，最终归因于呼吸力学的损害。响应烟曲霉攻击，Dectin-1−/− 小鼠表现出白细胞介素 (IL)-α、IL-1β、肿瘤坏死因子 (TNF)-α、CCL3/巨噬细胞炎症蛋白 (MIP)-α、CCL4/MIP-1β 和 CXCL1/KC 产生受损，导致肺中性粒细胞募集不足和烟曲霉肺部生长失控。 Dectin-1−/− 小鼠的肺泡巨噬细胞无法产生响应烟曲霉的促炎介质，而 Dectin-1−/− 小鼠的中性粒细胞活性氧生成受损，对烟曲霉的杀灭能力受损。我们进一步表明，烟曲霉攻击后肺部IL-17的产生是Dectin-1依赖性的，并且IL-17的中和显着损害了烟曲霉的清除。总的来说，这些结果支持 Dectin-1 在体内防御烟曲霉中的必要作用。
Immune suppression increases the incidence of invasive fungal infections, particularly those caused by the opportunistic mold Aspergillus fumigatus. Previous investigations revealed that members of the Toll-like receptor (TLR) family are not absolutely required for host defense against A. fumigatus in non-immunosuppressed hosts, suggesting that other pattern recognition receptors (PRRs) are involved. We show here that naive mice (i.e. not pharmacologically immunosuppressed) lacking the beta-glucan receptor Dectin-1 (Dectin-1−/−) are more sensitive to intratracheal challenge with A. fumigatus than control mice, exhibiting >80% mortality within 5 days, ultimately attributed to a compromise in respiratory mechanics. In response to A. fumigatus challenge, Dectin-1−/− mice demonstrated impaired interleukin (IL)-α, IL-1β, tumor necrosis factor (TNF)-α, CCL3/macrophage inflammatory protein (MIP)-α, CCL4/MIP-1β and CXCL1/KC production, which resulted in insufficient lung neutrophil recruitment and uncontrolled A. fumigatus lung growth. Alveolar macrophages from Dectin-1−/− mice failed to produce proinflammatory mediators in response to A. fumigatus, whereas neutrophils from Dectin-1−/− mice had impaired reactive oxygen species production and impaired killing of A. fumigatus. We further show that IL-17 production in the lung after A. fumigatus challenge was Dectin-1 dependent and that neutralization of IL-17 significantly impaired A. fumigatus clearance. Collectively, these results support a requisite role for Dectin-1 in in vivo defense against A. fumigatus.
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影响因子：
4.9
作者：
Bowman, JC;Abruzzo, GK;Douglas, CM
通讯作者：
Douglas, CM
影响因子：
4.4
作者：
Bellocchio, S;Montagnoli, C;Romani, L
通讯作者：
Romani, L
DOI：
10.1164/rccm.200704-606oc
发表时间：
2008-01-01
影响因子：
24.7
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
30.5
作者：
LeibundGut-Landmann, Salome;Gross, Olaf;Sousa, Caetano Reis e
通讯作者：
Sousa, Caetano Reis e