Rubino I Coste A Le Roy D Roger T Jaton K Boeckh M Monod M Latgé JP Calandra T Bochud PY 2012 BACKGROUND Aspergillus fumigatus causes invasive aspergillosis, a potentially fatal infection in oncohematological patients. Innate immune detection of A. fumigatus involves Toll-like receptor (TLR) 4 and TLR2, which forms a heterodimer with either TLR1 or TLR6. The role of those coreceptors in Aspergillus sensing is unknown. METHODS Cytokine production was measured in bone marrow-derived macrophages (BMDMs) from wild-type (WT) and TLR-deficient mice after incubation with a WT and an immunogenic RodA-deficient (ΔrodA-47) strain of A. fumigatus and in lungs from these mice after intranasal mold inoculation. Aspergillus fumigatus-mediated NF-κB activation was measured in HEK293T cells transfected with plasmids expressing mouse or human TLRs. RESULTS Bone marrow-derived macrophages from TLR1- and TLR6-deficient mice produced lower amounts of interleukin 12p40, CXCL2, interleukin 6, and tumor necrosis factor α than BMDMs from WT mice after stimulation with A. fumigatus. Lungs from TLR1- and TLR6-deficient mice had diminished CXCL1 and CXCL2 production and increased fungal burden after intranasal inoculation of ΔrodA A. fumigatus compared with lungs from WT mice. ΔrodA strain-mediated NF-κB activation was observed in HEK293T cells expressing mouse TLR2/1, mouse TLR2/6, and human TLR2/1 but not human TLR2/6. CONCLUSIONS Innate immune detection of A. fumigatus is mediated by TLR4 and TLR2 together with TLR1 or TLR6 in mice and TLR1 but not TLR6 in humans. application/pdf https://sonar.ch/global/documents/281214 eng info:eu-repo/semantics/altIdentifier/doi/10.1093/infdis/jir882 info:eu-repo/semantics/altIdentifier/pmid/22315281 info:eu-repo/semantics/openAccess The Journal of infectious diseases. - 2012 Animals Aspergillosis Aspergillus fumigatus Chemokine CXCL2 Female Gene Deletion HEK293 Cells Humans Immunity, Innate Interleukin-12 Subunit p40 Interleukin-6 Macrophages Mice Mice, Inbred C57BL NF-kappa B Species Specificity Toll-Like Receptor 1 Toll-Like Receptor 6 Tumor Necrosis Factor-alpha Species-specific recognition of Aspergillus fumigatus by Toll-like receptor 1 and Toll-like receptor 6. http://purl.org/coar/resource_type/c_6501