Marr Kieren A, Balajee S Arunmozhi, Hawn Thomas R, Ozinsky Adrian, Pham Uyenvy, Akira Shizuo, Aderem Alan, Liles W Conrad
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, 98109, USA.
Infect Immun. 2003 Sep;71(9):5280-6. doi: 10.1128/IAI.71.9.5280-5286.2003.
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.
Toll样受体介导巨噬细胞对微生物配体的识别，通过衔接蛋白MyD88诱导杀菌分子和细胞因子的表达。我们研究了MyD88在调节小鼠巨噬细胞对致病性酵母（白色念珠菌）和霉菌（烟曲霉）反应中的作用。与野生型（MyD88(+/+)）巨噬细胞相比，来自MyD88缺陷小鼠（MyD88(-/-)）骨髓的巨噬细胞对白色念珠菌的吞噬作用和细胞内杀伤能力受损。相比之下，烟曲霉分生孢子的摄取和杀伤不依赖MyD88。MyD88(-/-)巨噬细胞对白色念珠菌酵母和菌丝的细胞因子产生显著减少，但对烟曲霉菌丝的反应得以保留。这些结果证明MyD88信号传导参与了活的白色念珠菌的吞噬和杀伤，但不参与烟曲霉的吞噬和杀伤。MyD88的不同作用可能代表巨噬细胞调节针对不同致病真菌的固有反应的一种机制。
