Abstract
ABSTRACT
Awareness that fungal coinfection complicates viral respiratory infections
causing worse disease outcome has recently emerged. The environmental fungus
Aspergillus fumigatus
(Af) has been reported as the main driver of
fungal coinfection in patients suffering from viral infections caused by
Cytomegalovirus, Influenza or more recently SARS-CoV2. The airway epithelium is
the first common point of contact between inhaled pathogens and the host.
Aberrant airway epithelial cell (AEC) responses against fungal challenge have
been described in patients susceptible to aspergillosis. Therefore, it is likely
that a dysregulation of AEC responses during fungal-viral coinfection represents
a potent driver for the development of fungal disease. Here we used an
in vitro model of
Af-viral infection of AECs to determine outcomes of
spore internalisation, killing and viral replication during coinfection. Our
data indicate that viral stimulation, while boosting
Af uptake by AECs, limits
Af spore killing by those cells, favouring fungal
persistence and growth. Type I viral-induced interferon release was
significantly decreased in the presence of Af hyphal
forms suggesting a possible role of Af secreted
factors in modulating viral pathogenicity. We next explored the impact of
Af challenge in SARS-CoV2 replication within
airway epithelial cells using nano-luciferase as a measure of viral replication.
We found that Af increased SARS-CoV2 pathogenicity in
a strain-dependent manner. Collectively, our findings demonstrate a mutual
inhibition of antifungal and antiviral AEC responses during
Af-viral coinfection and also suggest that some
fungal factors might be key regulators of co-pathogenicity during in lung
infection.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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