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

The Candida albicans heat shock protein 90 kDa (hsp90-CA) is an important target for protective antibodies in disseminated candidiasis of experimental mice and humans. Hsp90-CA is present in the cell wall of Candida pseudohyphae or hyphae--typical pathogenic morphotypes in both mucosal and systemic Candida infections. However, the potential protective effects of hsp90-CA-specific antibodies in vaginal candidiasis has not yet been reported. In the present study we used various vaccine formulations (recombinant hsp90-CA protein and hsp90-CA-encoding DNA vaccine) and routes of administration (intradermal, intranasal, and intravenous) to induce both hsp90-CA-specific systemic and vaginal mucosa immune responses in experimental BALB/c mice. The results showed that intradermal recombinant hsp90-CA protein priming, followed by intranasal or intradermal recombinant hsp90-CA protein boosting induced significant increases in both serum and vaginal hsp90-CA-specific IgG and IgA antibodies compared to the control group, as well as enhanced hsp90-CA-specific splenocyte responses in vitro. In the intradermally boosted group, subsequent experimental vaginal Candida infection induced additional increases in the hsp90-CA specific IgG isotype, suggesting that Candida has the ability to induce a local hsp90-specific antibody (IgG) response during vulvovaginal candidiasis. Further work is required to elucidate the importance of immunity to highly conserved antigens during infection of the human female reproductive tract where a balance between immunity to and tolerance for commonly antigens such as hsp90 is necessary for the maintenance of fertility.

• MeSH
• aplikace intranazální MeSH
• Candida albicans imunologie   MeSH
• DNA vakcíny aplikace a dávkování   imunologie   MeSH
• financování organizované MeSH
• fungální proteiny imunologie   MeSH
• fungální vakcíny aplikace a dávkování   imunologie   MeSH
• injekce intradermální MeSH
• injekce intravenózní MeSH
• kandidóza vulvovaginální imunologie   MeSH
• lymfocyty imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• proliferace buněk MeSH
• proteiny tepelného šoku HSP90 imunologie   MeSH
• protilátky fungální analýza   krev   MeSH
• sekundární imunizace MeSH
• slezina imunologie   MeSH
• syntetické vakcíny aplikace a dávkování   imunologie   MeSH
• tvorba protilátek MeSH
• vagina imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

• MeSH
• aktiny MeSH
• finanční podpora výzkumu jako téma MeSH
• fungální proteiny analýza   imunologie   MeSH
• heterocyklické sloučeniny MeSH
• imunoblotting metody   MeSH
• lidé MeSH
• membránové proteiny chemie   imunologie   izolace a purifikace   MeSH
• Saccharomyces cerevisiae genetika   chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH