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Infection and Immunity, September 2003, p. 5280-5286, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5280-5286.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Differential Role of MyD88 in Macrophage-Mediated Responses to Opportunistic Fungal Pathogens

Fred Hutchinson Cancer Research Center,¹ University of Washington,² Institute for Systems Biology, Seattle, Washington,³ Osaka University, Osaka, Japan⁴

Received 17 January 2003/ Returned for modification 18 February 2003/ Accepted 19 June 2003

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.

Editor: T. R. Kozel

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