FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection
Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
HL080414
NHLBI NIH HHS - United States
P01 HL128191
NHLBI NIH HHS - United States
R01 AI065728
NIAID NIH HHS - United States
HL107191
NHLBI NIH HHS - United States
R01 HL080414
NHLBI NIH HHS - United States
R01 AI065728-01
NIAID NIH HHS - United States
U10 HL109146
NHLBI NIH HHS - United States
R01 AI113272
NIAID NIH HHS - United States
HL109146
NHLBI NIH HHS - United States
R01068150
PHS HHS - United States
R01 AI065495
NIAID NIH HHS - United States
P50 HL107191
NHLBI NIH HHS - United States
T32 GM007133
NIGMS NIH HHS - United States
PubMed
27058347
PubMed Central
PMC4825926
DOI
10.1371/journal.ppat.1005555
PII: PPATHOGENS-D-15-02698
Knihovny.cz E-zdroje
- 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
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.
Center for Synthesis and Chemical Biology University College Dublin Dublin Ireland
Department of Genetics University of Wisconsin Madison Madison Wisconsin
Department of Laboratory Medicine University of California San Francisco San Francisco California
Department of Medical Microbiology and Immunology University of Wisconsin Madison Madison Wisconsin
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