Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction

Peritoneal macrophages from Toll-like receptor (TLR) 4-deficient ScCr mice produced less tumor necrosis factor, interleukin (IL)-1alpha, and IL-1beta than did macrophages of control mice, when stimulated with conidia, but not with hyphae, of Aspergillus fumigatus, a finding suggesting that TLR4-medi...

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Veröffentlicht in:The Journal of infectious diseases Jg. 188; H. 2; S. 320
Hauptverfasser: Netea, Mihai G, Warris, Adilia, Van der Meer, Jos W M, Fenton, Matthew J, Verver-Janssen, Trees J G, Jacobs, Liesbeth E H, Andresen, Tonje, Verweij, Paul E, Kullberg, Bart Jan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 15.07.2003
Schlagworte:
Animals
Aspergillus fumigatus - immunology
Cell Line
Cytokines - immunology
Cytokines - metabolism
Fibroblasts
Humans
Hyphae - immunology
Inflammation - immunology
Inflammation - metabolism
Interleukin-10 - immunology
Interleukin-10 - metabolism
Macrophages - immunology
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Mice, Knockout
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Signal Transduction
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors
ISSN:0022-1899
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Zusammenfassung:Peritoneal macrophages from Toll-like receptor (TLR) 4-deficient ScCr mice produced less tumor necrosis factor, interleukin (IL)-1alpha, and IL-1beta than did macrophages of control mice, when stimulated with conidia, but not with hyphae, of Aspergillus fumigatus, a finding suggesting that TLR4-mediated signals are lost during germination. This hypothesis was confirmed by use of a TLR4-specific fibroblast reporter cell line (3E10) that responded to the conidia, but not to the hyphae, of A. fumigatus. In contrast, macrophages from TLR2-knockout mice had a decreased production of proinflammatory cytokines in response to both Aspergillus conidia and Aspergillus hyphae, and these results were confirmed in 3E10 cells transfected with human TLR2. In addition, Aspergillus hyphae, but not Aspergillus conidia, stimulated production of IL-10 through TLR2-dependent mechanisms. In conclusion, TLR4-mediated proinflammatory signals, but not TLR2-induced anti-inflammatory signals, are lost on Aspergillus germination to hyphae. Therefore, phenotypic switching during germination may be an important escape mechanism of A. fumigatus that results in counteracting the host defense.
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ISSN:0022-1899
DOI:10.1086/376456