Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

Stefan Bidula, Hany Kenawy, Youssif M. Ali, Darren Sexton, Wilhelm J. Schwaeble, Silke Schelenz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.
Original languageEnglish
Pages (from-to)1730-1740
Number of pages11
JournalInfection and Immunity
Volume81
Issue number5
Early online date11 Mar 2013
DOIs
Publication statusPublished - May 2013

Fingerprint

Mannose-Binding Lectin Complement Pathway
Aspergillus
Fungal Spores
Complement Activation
Collectins
Lectins
Mannose-Binding Lectin
Fungi
Aspergillus fumigatus
Epithelial Cells
Calcium
Acetylgalactosamine
Acetylglucosamine
Hyphae
Immunocompromised Host
ficolin
Interleukin-8
Cytokines
Inflammation

Cite this

Bidula, S., Kenawy, H., Ali, Y. M., Sexton, D., Schwaeble, W. J., & Schelenz, S. (2013). Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species. Infection and Immunity, 81(5), 1730-1740. https://doi.org/10.1128/IAI.00032-13

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species. / Bidula, Stefan; Kenawy, Hany; Ali, Youssif M.; Sexton, Darren; Schwaeble, Wilhelm J.; Schelenz, Silke.

In: Infection and Immunity, Vol. 81, No. 5, 05.2013, p. 1730-1740.

Research output: Contribution to journalArticle

Bidula, S, Kenawy, H, Ali, YM, Sexton, D, Schwaeble, WJ & Schelenz, S 2013, 'Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species', Infection and Immunity, vol. 81, no. 5, pp. 1730-1740. https://doi.org/10.1128/IAI.00032-13
Bidula, Stefan ; Kenawy, Hany ; Ali, Youssif M. ; Sexton, Darren ; Schwaeble, Wilhelm J. ; Schelenz, Silke. / Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species. In: Infection and Immunity. 2013 ; Vol. 81, No. 5. pp. 1730-1740.
@article{3d86127ab41e484e9838d5f76ed34d46,
title = "Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species",
abstract = "Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.",
author = "Stefan Bidula and Hany Kenawy and Ali, {Youssif M.} and Darren Sexton and Schwaeble, {Wilhelm J.} and Silke Schelenz",
note = "ACKNOWLEDGMENT This work was supported by the Medical Research Council, grant reference number G0801952.",
year = "2013",
month = "5",
doi = "10.1128/IAI.00032-13",
language = "English",
volume = "81",
pages = "1730--1740",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

AU - Bidula, Stefan

AU - Kenawy, Hany

AU - Ali, Youssif M.

AU - Sexton, Darren

AU - Schwaeble, Wilhelm J.

AU - Schelenz, Silke

N1 - ACKNOWLEDGMENT This work was supported by the Medical Research Council, grant reference number G0801952.

PY - 2013/5

Y1 - 2013/5

N2 - Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.

AB - Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.

U2 - 10.1128/IAI.00032-13

DO - 10.1128/IAI.00032-13

M3 - Article

VL - 81

SP - 1730

EP - 1740

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 5

ER -