title: Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis.
abstract: Aspergillus fumigatus, an opportunistic fungal pathogen, causes severe and usually fatal invasive pulmonary aspergillosis in immunocompromised hosts. Interestingly, Drosophila cells lacking the Toll protein are prone to A. fumigatus infection. In the current study, we looked for the involvement of Toll-like receptor 2 (TLR2) in the recognition of A. fumigatus by analyzing the in vivo and ex vivo responses of immunocompromised TLR2(-/-) and TLR2(+/+) mice to this fungus. Upon intratracheal administration of conidia, survival and tumor necrosis factor alpha (TNF-alpha), interleukin-12, and macrophage inhibitory protein-2 alpha concentrations in the airspaces of TLR2(-/-) mice were significantly lower than those of TLR2(+/+) animals. In vitro analysis of TNF-alpha production by conidia-challenged alveolar macrophages from TLR2(-/-) revealed a significant deficiency in comparison with macrophages from TLR2(+/+) mice. Infected TLR2(-/-) mice also have a higher respiratory distress and a higher pathogen burden than TLR2(+/+) mice. These data demonstrate that TLR2 plays a significant role in the defense of the host against A. fumigatus infection.
authors.affiliation: Unité de Défense Innée et Inflammation, Inserm E336, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Bruno
authors.initials: B
authors.lastname: Philippe
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Myriam
authors.initials: M
authors.lastname: Tanguy
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D054426:Chemokine CXCL2; D007113:Immunity, Innate / Q000235:genetics; D018664:Interleukin-12 / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000378:metabolism; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D015846:Monokines; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12