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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.<\/jats:p>","DOI":"10.4049\/jimmunol.2000802","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T15:00:13Z","timestamp":1603292413000},"page":"3058-3070","source":"Crossref","is-referenced-by-count":36,"title":["MDA5 Is an Essential Sensor of a Pathogen-Associated Molecular Pattern Associated with Vitality That Is Necessary for Host Resistance against\n                    <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2152-9045","authenticated-orcid":false,"given":"Xi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alayna K","family":"Caffrey-Carr","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"},{"name":"Department of Microbiology and Immunology, Montana State University , Bozeman, MT 59718"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-9101","authenticated-orcid":false,"given":"Ko-wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4808-3557","authenticated-orcid":false,"given":"Vanessa","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, Rutgers - New Jersey Medical School , Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walburga","family":"Croteau","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourabh","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-5597","authenticated-orcid":false,"given":"Amariliz","family":"Rivera","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, Rutgers - New Jersey Medical School , Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-5006","authenticated-orcid":false,"given":"Robert A","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-7911","authenticated-orcid":false,"given":"Joshua J","family":"Obar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2026041420283651500_r1","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1128\/JCM.36.6.1494-1500.1998","article-title":"Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings","volume":"36","author":"Chazalet","year":"1998","journal-title":"J. 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