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Dectin-1 Promotes Type I and III Interferon Expression to Support Optimal Antifungal Immunity in the Lung.
Frontiers in Cellular and Infection Microbiology ( IF 5.7 ) Pub Date : 2020-05-26 , DOI: 10.3389/fcimb.2020.00321
Orchi Dutta 1, 2 , Vanessa Espinosa 2 , Keyi Wang 1, 2 , Samantha Avina 1, 2 , Amariliz Rivera 3
Affiliation  

Pulmonary infections with Aspergillus fumigatus (Af) are a significant cause of invasive fungal disease and lead to high morbidity and mortality in diverse populations throughout the world. Currently available antifungal drugs are often ineffective, thus contributing to unacceptably high mortality rates in patients suffering from invasive fungal infections. The use of cytokines as adjunctive immune therapies holds the promise of significantly improving patient outcomes in the future. In recent studies, we identified an essential role for type I and III interferons as regulators of optimal antifungal responses by pulmonary neutrophils during infection with Af. Although various membrane and cytosolic nucleic acid sensors are known to regulate interferon production in response to viruses, the pathways that regulate the production of these cytokines during fungal infection remain uncovered. In the current study, we demonstrate that dectin-1-mediated recognition of β-glucan on the cell wall of the clinically relevant fungal pathogen Aspergillus fumigatus promotes the activation of a protective cascade of type I and III interferon expression. We further demonstrate that exogenous administration of type I and III interferons can rescue inadequate antifungal responses in dectin-1−/− mice, suggesting the potential therapeutic benefit of these cytokines as activators of antifungal defense in the context of innate defects.



中文翻译:

Dectin-1 促进 I 型和 III 型干扰素表达以支持肺中的最佳抗真菌免疫。

肺部感染 烟曲霉 (房颤) 是侵袭性真菌病的一个重要原因,并导致世界各地不同人群的高发病率和死亡率。目前可用的抗真菌药物通常无效,因此导致侵袭性真菌感染患者的死亡率高得令人无法接受。使用细胞因子作为辅助免疫疗法有望在未来显着改善患者的预后。在最近的研究中,我们确定了 I 型和 III 型干扰素作为肺中性粒细胞最佳抗真菌反应调节剂的重要作用。房颤. 尽管已知各种膜和胞质核酸传感器可调节干扰素的产生以响应病毒,但在真菌感染期间调节这些细胞因子产生的途径仍未发现。在目前的研究中,我们证明了 dectin-1 介导的对临床相关真菌病原体细胞壁上的 β-葡聚糖的识别烟曲霉促进 I 型和 III 型干扰素表达的保护级联的激活。我们进一步证明,外源性施用 I 型和 III 型干扰素可以挽救 dectin-1 -/-小鼠中不足的抗真菌反应,表明这些细胞因子作为先天缺陷情况下抗真菌防御激活剂的潜在治疗益处。

更新日期:2020-07-08
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