Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens

被引：90

作者：

Marr, KA

Balajee, SA

Hawn, TR

Ozinsky, A

Pham, U

Akira, S

Aderem, A

Liles, WC

机构：

[1] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[2] Inst Syst Biol, Seattle, WA USA

[3] Osaka Univ, Osaka, Japan

来源：

INFECTION AND IMMUNITY | 2003年 / 71卷 / 09期

关键词：

D O I：

10.1128/IAI.71.9.5280-5286.2003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：5280 / 5286

页数：7

共 35 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function
Adachi, O
Kawai, T
Takeda, K
Matsumoto, M
Tsutsui, H
Sakagami, M
Nakanishi, K
Akira, S
[J]. IMMUNITY, 1998, 9 (01) : 143 - 150
[2] Toll-like receptors in the induction of the innate immune response
Aderem, A
Ulevitch, RJ
[J]. NATURE, 2000, 406 (6797) : 782 - 787
[3] Mechanisms of phagocytosis in macrophages
Aderem, A
Underhill, DM
[J]. ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 : 593 - 623
[4] LIGATED COMPLEMENT RECEPTORS DO NOT ACTIVATE THE ARACHIDONIC-ACID CASCADE IN RESIDENT PERITONEAL-MACROPHAGES
ADEREM, AA
WRIGHT, SD
SILVERSTEIN, SC
COHN, ZA
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1985, 161 (03) : 617 - 622
[5] Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S
Takeda, K
Kaisho, T
[J]. NATURE IMMUNOLOGY, 2001, 2 (08) : 675 - 680
[6] Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L
Holt, AC
Medzhitov, R
Flavell, RA
[J]. NATURE, 2001, 413 (6857) : 732 - 738
[7] Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors
Brightbill, HD
Libraty, DH
Krutzik, SR
Yang, RB
Belisle, JT
Bleharski, JR
Maitland, M
Norgard, MV
Plevy, SE
Smale, ST
Brennan, PJ
Bloom, BR
Godowski, PJ
Modlin, RL
[J]. SCIENCE, 1999, 285 (5428) : 732 - 736
[8] Chinen T, 1999, CLIN EXP IMMUNOL, V115, P491
[9] Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
Fitzgerald, KA
Palsson-McDermott, EM
Bowie, AG
Jefferies, CA
Mansell, AS
Brady, G
Brint, E
Dunne, A
Gray, P
Harte, MT
McMurray, D
Smith, DE
Sims, JE
Bird, TA
O'Neill, LAJ
[J]. NATURE, 2001, 413 (6851) : 78 - 83
[10] β-1,2-linked oligomannosides from Candida albicans bind to a 32-kilodalton macrophage membrane protein homologous to the mammalian lectin galectin-3
Fradin, C
Poulain, D
Jouault, T
[J]. INFECTION AND IMMUNITY, 2000, 68 (08) : 4391 - 4398

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