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.

Základní údaje

Originální název

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

Autoři

KERR, Sheena C (840 Spojené státy), Gregory J FISCHER (840 Spojené státy), Meenal SINHA (840 Spojené státy), Orla MCCOBE (372 Irsko), Jonathan M. PALMER (840 Spojené státy), Tsokyi CHOERA (840 Spojené státy), Fang Yun LIM (840 Spojené státy), Michaela WIMMEROVÁ (203 Česká republika, garant, domácí), Stephen D. CARRINGTON (372 Irsko), Shaopeng YUAN (840 Spojené státy), Clifford A. LOWELL (840 Spojené státy), Stefan OSCARSON (372 Irsko), Nancy P. KELLER (840 Spojené státy) a John V. FAHY (840 Spojené státy)

Vydání

PLoS Pathog, 2016, 1553-7366

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 6.608

Kód RIV

RIV/00216224:14310/16:00088166

Organizační jednotka

Přírodovědecká fakulta

DOI

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

UT WoS

000378156900039

Klíčová slova anglicky

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

Štítky

AKR, rivok

Změněno: 6. 4. 2017 12:03, Ing. Andrea Mikešková

Anotace

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.

Návaznosti

GA13-25401S, projekt VaV

Název: Studium proteinů z patogenů zapojených do rozpoznávání hostitelského organismu

Investor: Grantová agentura ČR, Studium proteinu z patogenu zapojených do rozpoznávání hostitelského organismu

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 a John V. FAHY. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection. PLoS Pathog. 2016, roč. 12, č. 4, s. "nestrankovano", 20 s. ISSN 1553-7366. Dostupné z: 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 a 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, roč.~12, č.~4, s.~''nestrankovano'', 20 s. ISSN~1553-7366. Dostupné z: https://dx.doi.org/10.1371/journal.ppat.1005555.

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