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-1β proinflammatory responses in human mononuclear cells with suppression of IL-1β 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.

Additional Metadata
Keywords Aspergillus fumigatus, TLR4 protein, article, biosynthesis, conidium, controlled study, cytokine responsive element, down regulation, drug antagonism, fungal strain, fungus hyphae, fungus spore, human, immunological tolerance, immunology, immunomodulation, interleukin 1beta, interleukin 6, nonhuman, priority journal, toll like receptor 2, toll like receptor 4
Persistent URL dx.doi.org/10.1128/IAI.01455-08, hdl.handle.net/1765/16394
Citation
Chai, L.Y.A., Kullberg, B.J., Vonk, A.G., Warris, A., Cambi, A., Latgé, J.P., … Netea, M.G.. (2009). Modulation of toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus. Infection and Immunity, 77(5), 2184–2192. doi:10.1128/IAI.01455-08