The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia.

• MeSH
• Aspergillus fumigatus imunologie   patogenita   MeSH
• dospělí MeSH
• fluorescenční protilátková technika MeSH
• fukosa metabolismus   MeSH
• fungální proteiny imunologie   metabolismus   MeSH
• lektiny imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• muciny imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• plicní aspergilóza imunologie   metabolismus   MeSH
• průtoková cytometrie MeSH
• slizniční imunita imunologie   MeSH
• spory hub imunologie   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fucose-binding lectin MeSH Prohlížeč
• fukosa MeSH
• fungální proteiny MeSH
• lektiny MeSH
• muciny MeSH