Modulation of Toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus.
Toll-like receptor (TLR)-based signaling pathways in the host may be modulated by pathogens during the course of infection. We describe a novel immunomodulatory mechanism in which Aspergillus fumigatus conidia induce attenuation of TLR2- and TLR4-mediated interleukin (IL)-6 and IL-1beta proinflammatory responses in human mononuclear cells with suppression of IL-1beta mRNA transcription. Background TLR2 and TLR4 mRNA transcription was not influenced. A. fumigatus conidia induced TLR2 internalization and uptake into the phagosome with a resultant decrease in surface receptor expression. A. fumigatus hyphae, on the other hand, selectively downregulated the TLR4-mediated response. These novel immunosuppressive effects may facilitate the invasiveness of A. fumigatus.
Chai
Louis Y A
LY
Department of Medicine (463), Radboud University Nijmegen Medical Center, P.O. Box 9101, Geert Grootplein 8, 6525 GA Nijmegen, The Netherlands.
Kullberg
Bart Jan
BJ
Vonk
Alieke G
AG
Warris
Adilia
A
Cambi
Alessandra
A
Latgé
Jean-Paul
JP
Joosten
Leo A B
LA
van der Meer
Jos W M
JW
Netea
Mihai G
MG
D001232:Aspergillus fumigatus / Q000276:immunology*; D006801:Humans; D025301:Hyphae / Q000276:immunology; D007108:Immune Tolerance; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D013172:Spores, Fungal / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
D053583:Interleukin-1beta; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000093242:Interleukin-6 Inhibitors; C495345:TLR4 protein, human