title: Recognition of yeast nucleic acids triggers a host-protective type I interferon response.
abstract: Although type I interferons (IFN-α/β) have been traditionally associated with antiviral responses, their importance in host defense against bacterial pathogens is being increasingly appreciated. Little is known, however, about the occurrence and functional role of IFN-α/β production in response to pathogenic yeasts. Here, we found that conventional DCs, but not macrophages nor plasmacytoid DCs, mounted IFN-β responses after in vitro stimulation with Candida spp. or Saccharomyces cerevisiae. These responses absolutely required MyD88, a Toll-like receptor (TLR) adaptor molecule, and were partially dependent on TLR9 and TLR7. Moreover, Candida DNA, as well as RNA, could recapitulate the IFN-β response. After intravenous challenge with Candida albicans, most mice lacking the IFN-α/β receptor died from their inability to control fungal growth, whereas all WT controls survived. These data suggest that recognition of yeast nucleic acids by TLR7 and TLR9 triggers a host-protective IFN-α/β response.
authors.affiliation: The Elie Metchnikoff Department, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Biondo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Signorino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
authors.forename: Angelina
authors.initials: A
authors.lastname: Midiri
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gerace
authors.forename: Roberta
authors.initials: R
authors.lastname: Galbo
authors.forename: Antonella
authors.initials: A
authors.lastname: Bellantoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Malara
authors.forename: Concetta
authors.initials: C
authors.lastname: Beninati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D004271:DNA, Fungal / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012331:RNA, Fungal / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D007370:Interferon Type I; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012331:RNA, Fungal; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D016899:Interferon-beta