title: Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens.
abstract: Toll-like receptors mediate macrophage recognition of microbial ligands, inducing expression of microbicidal molecules and cytokines via the adapter protein MyD88. We investigated the role of MyD88 in regulating murine macrophage responses to a pathogenic yeast (Candida albicans) and mold (Aspergillus fumigatus). Macrophages derived from bone marrow of MyD88-deficient mice (MyD88(-/-)) demonstrated impaired phagocytosis and intracellular killing of C. albicans compared to wild-type (MyD88(+/+)) macrophages. In contrast, ingestion and killing of A. fumigatus conidia was MyD88 independent. Cytokine production by MyD88(-/-) macrophages in response to C. albicans yeasts and hyphae was substantially decreased, but responses to A. fumigatus hyphae were preserved. These results provide evidence that MyD88 signaling is involved in phagocytosis and killing of live C. albicans, but not A. fumigatus. The differential role of MyD88 may represent one mechanism by which macrophages regulate innate responses specific to different pathogenic fungi.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington, Seattle, 98109, USA. kmarr@fhcrc.org
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
authors.forename: S Arunmozhi
authors.initials: SA
authors.lastname: Balajee
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
authors.forename: Adrian
authors.initials: A
authors.lastname: Ozinsky
authors.forename: Uyenvy
authors.initials: U
authors.lastname: Pham
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D001228:Aspergillosis / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000472:pathogenicity; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009181:Mycoses / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D009894:Opportunistic Infections / Q000276:immunology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic