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

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2003 Aug 23

PMID 12933875

Citations 29

Authors

Kieren A Marr

S Arunmozhi Balajee

Thomas R Hawn

Adrian Ozinsky

Uyenvy Pham

Shizuo Akira

Alan Aderem

W Conrad Liles

Affiliations

Soon will be listed here.

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.

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