Analysis of the interactions between bronchial cells and Aspergillus fumigatus

Ref ID: 19367

Author:

A. Fekkar,1 C. Canivet,2 V. Balloy,3 A. Datry,4 M. Chignard3 and
D. Mazier2

Author address:

1H^opital de La Piti!e-Salp^etriere, Paris, France

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Aspergillus fumigatus is a major mold pathogen responsible
for a broad variety of diseases in both immunocompetent and immuno-
compromised patients. Innate immunity is considered as fundamental
for host defenses against the fungus. For years, studies have mainly
been focused on polymorphonuclear cells, macrophages or mast cells.
However, epithelial cells such as bronchial cells are increasingly con-
sidered as important effectors against this fungal infection, but little is
known about interactions between bronchial cells and the fungus.
We first investigated the secretome of bronchial epithelial cells
infected by A. fumigatus using an original proteomic approach by
DIGE. Our study uncovered unexpected aspects of bronchial cell
behavior in relation to Aspergillus infection: in response to the fungal
aggression, bronchial cells are notably able to develop immune reac-
tions by lysosomal degranulation and cathepsin B activation, a
mechanism that was thought to be reserved for professional cells
such as mast cells (Fekkar et al J Infect Dis 2012). To add depth to
the understanding of the reaction process of the bronchial barrier
when in contact with the growing fungus, we studied the potential
role of cathepsin B in the release of interleukin 8 and in the forma-
tion of inflammasome.
Methods We used the human bronchial cell line BEAS-2B infected
by Aspergillus fumigatus during a 15-hour co-culture. Experiments
included DIGE analysis, transcriptome and western blot analysis as
well as measure of interleukins in the culture supernatants.
Results Using quantification gene expression by RTqPCR we showed
that Aspergillus fumigatus induced up-regulation of IL-8, IL-1 beta,
and IL-18 gene expression by the human bronchial cell line BEAS-
2B. Using different inhibitors, we also showed that IL-8 secretion by
human bronchial cells infected by A. fumigatus was dependant on
cathepsin B activity.
Moreover, we found that Aspergillus fumigatus induces ASC activa-
tion in human bronchial cell line. ASC is an adaptor protein which
plays an important role in the activation of the multiprotein platform
inflammasome that leads to the production of IL1b an IL18. Finally,
ASC activation in response to A. fumigatus was also dependant on
cathepsin B activity.
Conclusion Our study reveals new aspects of bronchial cell behavior
in relation to Aspergillus infection. Indeed, we showed that bronchial
epithelial cells released IL-8 in response to Aspergillus infection through
a cathepsin B dependant mechanism. We also demonstrated that the
bronchial cells participate to fungal defense by activating part of the
inflammasome and up-regulating IL1b and IL18 gene expression.
Therefore bronchial epithelial cells appear to be a more important
effector of antifungal defense than expected.

Conference Year: 2013

Link to conference website: NULL

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