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

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Authors

KERR Sheena C FISCHER Gregory J SINHA Meenal MCCOBE Orla PALMER Jonathan M. CHOERA Tsokyi LIM Fang Yun WIMMEROVÁ Michaela CARRINGTON Stephen D. YUAN Shaopeng LOWELL Clifford A. OSCARSON Stefan KELLER Nancy P. FAHY John V.

Year of publication 2016
Type Article in Periodical
Magazine / Source PLoS Pathog
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1371/journal.ppat.1005555
Field Biochemistry
Keywords FUCOSE-BINDING LECTIN; PSEUDOMONAS-AERUGINOSA; ALEURIA-AURANTIA; RALSTONIA-SOLANACEARUM; ALVEOLAR MACROPHAGES; DECTIN-1; RESPONSES; CONIDIA; SPECIFICITY; INVOLVEMENT
Description Inhaled Aspergillus fumigatus conidia are effectively eliminated from the lung by the coordinated actions of mucociliary clearance and macrophage killing, but the mechanisms of attachment of Aspergillus fumigatus (A. fumigatus) conidia to the airway mucus gel are unknown. In addition, the mechanisms of phagocytosis of conidia by macrophages are incompletely understood, because inhibition of Dectin-1, mannose receptor, and TLR-2/4 does not completely prevent phagocytosis. A fucose-binding lectin (FleA) expressed on the surface of Aspergillus conidia has recently been described, but its function is unknown. In order to reveal FleA’s function, we carried out combined in vitro and in vivo studies using several novel reagents, including recombinant FleA, FleA deficient (deltafleA) conidia and a potent fucopyranoside inhibitor of FleA. In vitro studies found that FleA mediates binding of A. fumigatus conidia to airway mucins and phagocytosis of conidia by lung macrophages. In in vivo studies we found that mice infected with deltafleA conidia develop invasive aspergillosis whereas those exposed to WT conidia do not. Based on our findings, we propose a novel host defense mechanism against A. fumigatus in which FleA expression on conidia is recognized by lung mucins and macrophages to promote mucociliary clearance and macrophage killing and protect from invasive pulmonary aspergillosis.
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