FIBCD1 binds to Aspergillus fumigatus chitin and modulates the inflammatory response induced by cell wall polysaccharides , proteases and intact organism

Ref ID: 19592

Author:

LK Dubey1,2*, JB Moeller1, CS Jespen1, MA Hammond1, A Schlosser1, GL Sorensen1,
U Holmskov1

Author address:

1Department of Cardiovascular and Renal Research, Denmark, University of Southern Denmark, Odense,
Denmark
2Global Health Institute, EPFL, Lausanne, Switzerland

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Aim:
We have recently identified and characterized fibrinogen C domain-containing protein 1
(FIBCD1) as a homotetrameric type II transmembrane protein expressed by epithelial cells.
In the present study, we investigate the role of FIBCD1 in the immune reaction against Aspergillus
fumigatus (A. fumigatus), a pathogenic fungus involved in the development of asthma and allergy
in western society. We try to understand the collective and individual role of fungal cell wall
polysaccharides i.e. chitin and b-glucan and propose FIBCD1 as a novel Pattern Recognition
Receptors (PRRs) which can recognize fungal cell wall chitin and modulate the innate immune
response.
Methods:
We eutilized fluroscence microscopy, pull down binding assays along with in vitro stimulation
studies to test our hypothesis which were further confirmed using in vivo studies.
Results:
We show that FIBCD1 binds to the A. fumigatus cell wall, which is primarily composed of chitin,
b-glucan, and galactomannan, in a calcium- and acetate-independent manner. We demonstrate that
FIBCD1 recognises chitin-rich zones in the fungal cell wall in different cellular stages of A. fumigatus
and that FIBCD1 is expressed in ciliated airway epithelial cells from patients with aspergillosis. We
show that conidia, AIF, chitin, and b-glucan induce IL-8 secretion from A549 lung epithelial cells
in a time- and dose-dependent manner. Furthermore, our results indicate that FIBCD1-transfected
A549 cells display reduced IL-8 secretion compared to sham-transfected A549 cells when stimulated
with any of these cell wall preparation and that this reduction is significantly increased when the
polysaccharide is a FIBCD1 ligand. Furthermore, to evaluate the role of A. fumigatus chitin, which
binds to FIBCD1, we studied the role of alkali insoluble polysaccharides in vivo. We demonstrated
that Aspergillus fumigatus alkali-insoluble cell wall fragments (AIF) induced enhanced immune
responses when compared with individual cell wall polysaccharides. Intranasal administration of
AIF induced eosinophil and neutrophil recruitment, chitinase activity, TNF-α and TSLP production
in mice lungs. Selective destruction of chitin or β -glucan from AIF significantly reduced eosinophil
and neutrophil recruitment as well as chitinase activity and cytokine expression by macrophages,
indicating the synergistic effect of the cell wall polysaccharides when presented together as a
composite PAMP.
Conclusion:
Collectively our in vivo and in vitro data indicate that chitin and β -glucan play an important roles in
activating innate immunity when presented as composite cell wall PAMPs and FIBCD1 is present
in human airway epithelial cells, binds A. fumigatus cell wall PAMPs i.e chitin and influences the
inflammatory response in the lung.

Abstract Number: 117

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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