FIBCD1 Binds Aspergillus fumigatus and Regulates Lung Epithelial Response to Cell Wall Components
Christine Schoeler Jepsen1, Lalit Kumar Dubey1,2, Kimmie B Colmorten1
1Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
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.
Insights
Fibrinogen C domain-containing protein 1 (FIBCD1) recognizes Aspergillus fumigatus cell walls in the human lung. FIBCD1 suppresses inflammatory responses and mucin production in lung epithelial cells.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Aspergillus fumigatus is a common fungus causing lung diseases.
- Fibrinogen C domain-containing protein 1 (FIBCD1) binds chitin and is found in the gut and salivary glands.
- The role of FIBCD1 in the human lung and its interaction with A. fumigatus is not well understood.
Purpose of the Study:
- To investigate FIBCD1 expression in human lung epithelium.
- To determine if FIBCD1 recognizes Aspergillus fumigatus cell wall components.
- To elucidate the functional role of FIBCD1 in modulating lung epithelial inflammatory responses.
Main Methods:
- Immunohistochemistry to localize FIBCD1 in human lung tissue.
- Cell-based assays using FIBCD1-transfected lung epithelial cells stimulated with A. fumigatus components.
- Measurement of inflammatory mediators (e.g., IL-8) and mucin production.
- Analysis of gene transcription related to inflammation and homeostasis.
Main Results:
- FIBCD1 is expressed on the surface of human bronchial and alveolar epithelial cells.
- FIBCD1 recognizes Aspergillus fumigatus cell wall polysaccharides independently of its chitin-binding site.
- FIBCD1 suppresses IL-8 secretion, mucin production, and inflammatory gene expression in response to A. fumigatus stimulation.
- FIBCD1 modulates IL-8 secretion induced by Toll-like receptors (TLR2, -4, and -5).
Conclusions:
- FIBCD1 functions as a pattern recognition receptor in the human lung epithelium.
- FIBCD1 recognizes complex polysaccharides of the Aspergillus fumigatus cell wall.
- FIBCD1 plays a role in modulating the lung epithelial inflammatory response to fungal components by suppressing inflammatory mediators and mucins.
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