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

J 2016

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

KERR, Sheena C, Gregory J FISCHER, Meenal SINHA, Orla MCCOBE, Jonathan M. PALMER et. al.

Basic information

Original name

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

Authors

KERR, Sheena C (840 United States of America), Gregory J FISCHER (840 United States of America), Meenal SINHA (840 United States of America), Orla MCCOBE (372 Ireland), Jonathan M. PALMER (840 United States of America), Tsokyi CHOERA (840 United States of America), Fang Yun LIM (840 United States of America), Michaela WIMMEROVÁ (203 Czech Republic, guarantor, belonging to the institution), Stephen D. CARRINGTON (372 Ireland), Shaopeng YUAN (840 United States of America), Clifford A. LOWELL (840 United States of America), Stefan OSCARSON (372 Ireland), Nancy P. KELLER (840 United States of America) and John V. FAHY (840 United States of America)

Edition

PLoS Pathog, 2016, 1553-7366

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 6.608

RIV identification code

RIV/00216224:14310/16:00088166

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1371/journal.ppat.1005555

UT WoS

000378156900039

Keywords in English

FUCOSE-BINDING LECTIN; PSEUDOMONAS-AERUGINOSA; ALEURIA-AURANTIA; RALSTONIA-SOLANACEARUM; ALVEOLAR MACROPHAGES; DECTIN-1; RESPONSES; CONIDIA; SPECIFICITY; INVOLVEMENT

Abstract

V originále

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.

Links

GA13-25401S, research and development project

Name: Studium proteinů z patogenů zapojených do rozpoznávání hostitelského organismu

Investor: Czech Science Foundation

Citovat

KERR, Sheena C, Gregory J FISCHER, Meenal SINHA, Orla MCCOBE, Jonathan M. PALMER, Tsokyi CHOERA, Fang Yun LIM, Michaela WIMMEROVÁ, Stephen D. CARRINGTON, Shaopeng YUAN, Clifford A. LOWELL, Stefan OSCARSON, Nancy P. KELLER and John V. FAHY. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection. PLoS Pathog. 2016, vol. 12, No 4, p. "nestrankovano", 20 pp. ISSN 1553-7366. Available from: https://dx.doi.org/10.1371/journal.ppat.1005555.

@article{1354567,
   author = {Kerr, Sheena C and Fischer, Gregory J and Sinha, Meenal and McCobe, Orla and Palmer, Jonathan M. and Choera, Tsokyi and Lim, Fang Yun and Wimmerová, Michaela and Carrington, Stephen D. and Yuan, Shaopeng and Lowell, Clifford A. and Oscarson, Stefan and Keller, Nancy P. and Fahy, John V.},
   article_number = {4},
   doi = {http://dx.doi.org/10.1371/journal.ppat.1005555},
   keywords = {FUCOSE-BINDING LECTIN; PSEUDOMONAS-AERUGINOSA; ALEURIA-AURANTIA; RALSTONIA-SOLANACEARUM; ALVEOLAR MACROPHAGES; DECTIN-1; RESPONSES; CONIDIA; SPECIFICITY; INVOLVEMENT},
   language = {eng},
   issn = {1553-7366},
   journal = {PLoS Pathog},
   title = {FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection},
   volume = {12},
   year = {2016}
}

TY  - JOUR
ID  - 1354567
AU  - 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.
PY  - 2016
TI  - FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection
JF  - PLoS Pathog
VL  - 12
IS  - 4
SP  - "nestrankovano"
EP  - "nestrankovano"
SN  - 15537366
KW  - FUCOSE-BINDING LECTIN
KW  - PSEUDOMONAS-AERUGINOSA
KW  - ALEURIA-AURANTIA
KW  - RALSTONIA-SOLANACEARUM
KW  - ALVEOLAR MACROPHAGES
KW  - DECTIN-1
KW  - RESPONSES
KW  - CONIDIA
KW  - SPECIFICITY
KW  - INVOLVEMENT
N2  - 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.
ER  -

KERR, Sheena C, Gregory J FISCHER, Meenal SINHA, Orla MCCOBE, Jonathan M. PALMER, Tsokyi CHOERA, Fang Yun LIM, Michaela WIMMEROVÁ, Stephen D. CARRINGTON, Shaopeng YUAN, Clifford A. LOWELL, Stefan OSCARSON, Nancy P. KELLER and John V. FAHY. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection. \textit{PLoS Pathog}. 2016, vol.~12, No~4, p.~''nestrankovano'', 20 pp. ISSN~1553-7366. Available from: https://dx.doi.org/10.1371/journal.ppat.1005555.

Detailed Information on Publication Record