FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection

. 2016 Apr ; 12 (4) : e1005555. [epub] 20160408

Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid27058347

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

Odkazy

PubMed 27058347
PubMed Central PMC4825926
DOI 10.1371/journal.ppat.1005555
PII: PPATHOGENS-D-15-02698
Knihovny.cz E-zdroje

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.

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