FIBCD1 binds aspergillus fumigatus and regulates lung epithelial response to cell wall components

Christine Schoeler Jepsen, Lalit Kumar Dubey, Kimmie B. Colmorten, Jesper B. Moeller, Mark A. Hammond, Ole Nielsen, Anders Schlosser, Steven Templeton, Grith L. Sorensen, Uffe Holmskov

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aspergillus fumigatus (A. fumigatus) is a ubiquitous fungus of clinical importance associated with development of various pulmonary diseases and allergic hypersensitivity reactions. It is protected against environmental stress by a cell wall that contains polysaccharides such as chitin. We previously demonstrated that fibrinogen C domain-containing protein 1 (FIBCD1) is a membrane-bound protein that binds chitin through a conserved S1 binding site and is expressed in intestinal epithelium and salivary glands. Here, we further localized FIBCD1 protein expression at the surface of bronchial and alveolar human lung epithelium, observed recognition of A. fumigatus cell wall with S1 site-independent recognition. We observed FIBCD1-mediated suppression of IL-8 secretion, mucin production, and transcription of genes associated with airway inflammation and homeostasis in FIBCD1-transfected lung epithelial cells. These modulations were generally enforced by stimulation with A. fumigatus cell wall polysaccharides. In parallel, we demonstrated a FIBCD1-mediated modulation of IL-8 secretion induced by TLR2,−4, and −5. Collectively, our findings support FIBCD1 as a human lung epithelial pattern recognition receptor that recognizes the complex A. fumigatus cell wall polysaccharides and modulates the lung epithelial inflammatory response by suppressing inflammatory mediators and mucins.

Aspergillus fumigatus (A. fumigatus) is a ubiquitous fungus of clinical importance associated with development of various pulmonary diseases and allergic hypersensitivity reactions. It is protected against environmental stress by a cell wall that contains polysaccharides such as chitin. We previously demonstrated that fibrinogen C domain-containing protein 1 (FIBCD1) is a membrane-bound protein that binds chitin through a conserved S1 binding site and is expressed in intestinal epithelium and salivary glands. Here, we further localized FIBCD1 protein expression at the surface of bronchial and alveolar human lung epithelium, observed recognition of A. fumigatus cell wall with S1 site-independent recognition. We observed FIBCD1-mediated suppression of IL-8 secretion, mucin production, and transcription of genes associated with airway inflammation and homeostasis in FIBCD1-transfected lung epithelial cells. These modulations were generally enforced by stimulation with A. fumigatus cell wall polysaccharides. In parallel, we demonstrated a FIBCD1-mediated modulation of IL-8 secretion induced by TLR2,−4, and −5. Collectively, our findings support FIBCD1 as a human lung epithelial pattern recognition receptor that recognizes the complex A. fumigatus cell wall polysaccharides and modulates the lung epithelial inflammatory response by suppressing inflammatory mediators and mucins.

Original languageEnglish (US)
Article number1967
JournalFrontiers in Immunology
Volume9
Issue numberSEP
DOIs
StatePublished - Sep 18 2018
Externally publishedYes

Fingerprint

Aspergillus fumigatus
Cellular Structures
Fibrinogen
Cell Wall
Lung
Polysaccharides
Chitin
Mucins
Intestinal Mucosa
Interleukin-8
Hypersensitivity
Pattern Recognition Receptors
Salivary Glands
Lung Diseases
Protein Domains
Membrane Proteins
Homeostasis
Fungi
Epithelium
Epithelial Cells

Keywords

  • A549
  • Aspergillus fumigatus
  • Epithelium
  • FIBCD1
  • Human
  • IL-8
  • Inflammation
  • Lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Jepsen, C. S., Dubey, L. K., Colmorten, K. B., Moeller, J. B., Hammond, M. A., Nielsen, O., ... Holmskov, U. (2018). FIBCD1 binds aspergillus fumigatus and regulates lung epithelial response to cell wall components. Frontiers in Immunology, 9(SEP), [1967]. https://doi.org/10.3389/fimmu.2018.01967

FIBCD1 binds aspergillus fumigatus and regulates lung epithelial response to cell wall components. / Jepsen, Christine Schoeler; Dubey, Lalit Kumar; Colmorten, Kimmie B.; Moeller, Jesper B.; Hammond, Mark A.; Nielsen, Ole; Schlosser, Anders; Templeton, Steven; Sorensen, Grith L.; Holmskov, Uffe.

In: Frontiers in Immunology, Vol. 9, No. SEP, 1967, 18.09.2018.

Research output: Contribution to journalArticle

Jepsen, CS, Dubey, LK, Colmorten, KB, Moeller, JB, Hammond, MA, Nielsen, O, Schlosser, A, Templeton, S, Sorensen, GL & Holmskov, U 2018, 'FIBCD1 binds aspergillus fumigatus and regulates lung epithelial response to cell wall components', Frontiers in Immunology, vol. 9, no. SEP, 1967. https://doi.org/10.3389/fimmu.2018.01967
Jepsen, Christine Schoeler ; Dubey, Lalit Kumar ; Colmorten, Kimmie B. ; Moeller, Jesper B. ; Hammond, Mark A. ; Nielsen, Ole ; Schlosser, Anders ; Templeton, Steven ; Sorensen, Grith L. ; Holmskov, Uffe. / FIBCD1 binds aspergillus fumigatus and regulates lung epithelial response to cell wall components. In: Frontiers in Immunology. 2018 ; Vol. 9, No. SEP.
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AU - Dubey, Lalit Kumar

AU - Colmorten, Kimmie B.

AU - Moeller, Jesper B.

AU - Hammond, Mark A.

AU - Nielsen, Ole

AU - Schlosser, Anders

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KW - A549

KW - Aspergillus fumigatus

KW - Epithelium

KW - FIBCD1

KW - Human

KW - IL-8

KW - Inflammation

KW - Lung

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