Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens.
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.
Marr
Kieren A
KA
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, 98109, USA. kmarr@fhcrc.org
Balajee
S Arunmozhi
SA
Hawn
Thomas R
TR
Ozinsky
Adrian
A
Pham
Uyenvy
U
Akira
Shizuo
S
Aderem
Alan
A
Liles
W Conrad
WC
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
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic