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

• DOI: 10.1371/journal.ppat.1005555
• Publication Date: 2016-04-09T01:37:59Z
• Authors: Sheena C. Kerr; Gregory J. Fischer; Meenal Sinha; Orla McCabe; Jonathan M. Palmer; Tsokyi Choera; Fang Yun Lim; Michaela Wimmerova; Stephen D. Carrin...; Shaopeng Yuan; Clifford A. Lowell; Stefan Oscarson; Nancy P. Keller; John V. Fahy
• Keywords: Virulence factor

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