RT Journal Article SR Electronic T1 MDA5 is an essential vita-PAMP sensor necessary for host resistance against Aspergillus fumigatus JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.06.182154 DO 10.1101/2020.07.06.182154 A1 Xi Wang A1 Alayna K. Caffrey-Carr A1 Ko-wei Liu A1 Vanessa Espinosa A1 Walburga Croteau A1 Sourabh Dhingra A1 Amariliz Rivera A1 Robert A. Cramer A1 Joshua J. Obar YR 2020 UL http://biorxiv.org/content/early/2020/07/06/2020.07.06.182154.abstract AB RIG-I like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor to activate interferon responses against viruses. Whether the RLR family has broader effects on host immunity against other pathogen families remains to be fully explored. Herein we demonstrate that MDA5/MAVS signaling was essential for host resistance against pulmonary Aspergillus fumigatus challenge through the regulation of antifungal leukocyte responses. 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 interferons after A. fumigatus challenge was only partially dependent on MDA5/MAVS signaling, whereas type III interferon expression was entirely dependent on MDA5/MAVS signaling. Ultimately, type I and III interferon signaling drove the expression of CXCL10, which is critical in resistance against invasive aspergillosis in transplant patients. Furthermore, the MDA5/MAVS-dependent interferon 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.Competing Interest StatementThe authors have declared no competing interest.