Key Points MDA5 is essential for maintaining host resistance against A. fumigatus. MDA5 serves as a critical vitality sensor after fungal challenge. MDA5 is essential for IFN-λ expression and antifungal neutrophil killing. Visual Abstract RIG-I–like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate IFN responses against viruses. Whether the RLR family has broader effects on host immunity against other pathogen families remains to be fully explored. In this study, we demonstrate that MDA5/MAVS signaling was essential for host resistance against pulmonary Aspergillus fumigatus challenge through the regulation of antifungal leukocyte responses in mice. Activation of MDA5/MAVS signaling was driven by dsRNA from live A. fumigatus serving as a key vitality-sensing pattern recognition receptor. Interestingly, induction of type I IFNs after A. fumigatus challenge was only partially dependent on MDA5/MAVS signaling, whereas type III IFN expression was entirely dependent on MDA5/MAVS signaling. Ultimately, type I and III IFN signaling drove the expression of CXCL10. Furthermore, the MDA5/MAVS-dependent IFN response was critical for the induction of optimal antifungal neutrophil killing of A. fumigatus spores. In conclusion, our data broaden the role of the RLR family to include a role in regulating antifungal immunity against A. fumigatus.

中文翻译：

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MDA5 是病原体相关分子模式的基本传感器，与生命力相关，是宿主对烟曲霉的抗性所必需的

要点 MDA5 对于维持宿主对烟曲霉的抗性至关重要。MDA5 作为真菌挑战后的关键活力传感器。MDA5 对于 IFN-λ 表达和抗真菌中性粒细胞杀伤至关重要。Visual Abstract RIG-I 样受体 (RLR) 是胞质 RNA 传感器，通过 MAVS 适配器发出信号以激活针对病毒的 IFN 反应。RLR 家族是否对宿主对其他病原体家族的免疫有更广泛的影响仍有待充分探索。在这项研究中，我们证明 MDA5/MAVS 信号通过调节小鼠的抗真菌白细胞反应对宿主抵抗肺烟曲霉攻击至关重要。MDA5/MAVS 信号的激活由来自活烟曲霉的 dsRNA 驱动，作为关键的活力感应模式识别受体。有趣的是，烟曲霉攻击后 I 型 IFN 的诱导仅部分依赖于 MDA5/MAVS 信号，而 III 型 IFN 表达完全依赖于 MDA5/MAVS 信号。最终，I 型和 III 型 IFN 信号驱动 CXCL10 的表达。此外，MDA5/MAVS 依赖性 IFN 反应对于诱导最佳抗真菌嗜中性粒细胞杀死烟曲霉孢子至关重要。总之，我们的数据扩大了 RLR 家族的作用，包括在调节针对烟曲霉的抗真菌免疫中的作用。MDA5/MAVS 依赖性 IFN 反应对于诱导最佳抗真菌嗜中性粒细胞杀死烟曲霉孢子至关重要。总之，我们的数据扩大了 RLR 家族的作用，包括在调节针对烟曲霉的抗真菌免疫中的作用。MDA5/MAVS 依赖性 IFN 反应对于诱导最佳抗真菌嗜中性粒细胞杀死烟曲霉孢子至关重要。总之，我们的数据扩大了 RLR 家族的作用，包括在调节针对烟曲霉的抗真菌免疫中的作用。