Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis.
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.
Balloy
Viviane
V
Unité de Défense Innée et Inflammation, Inserm E336, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France.
Si-Tahar
Mustapha
M
Takeuchi
Osamu
O
Philippe
Bruno
B
Nahori
Marie-Anne
MA
Tanguy
Myriam
M
Huerre
Michel
M
Akira
Shizuo
S
Latgé
Jean-Paul
JP
Chignard
Michel
M
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
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