Aspergillus fumigatus causes in vitro electrophysiological and morphological modifications in human nasal epithelial cells F. Botterel1,2, C. Cordonnier3,4, V. Barbier1, L. Wingerstmann3, M. Liance1, A. Coste3,5, E. Escudier3,6 and S. Bretagne1 1Laboratoire de Parasitologie-Mycologie, Hôpital Henri Mondor (AP-HP) and UMR-BIPAR Université Paris XII, 94010, Créteil, France, 2Laboratoire de Microbiologie, Hôpital du Kremlin-Bicêtre (AP-HP), France, 3Inserm U 492, Université Paris XII, Créteil, France, 4Service d'Hématologie Clinique, Hôpital Henri Mondor (AP-HP), Créteil, France and 5Service d'ORL et de Chirurgie Cervico-faciale, Hôpital Henri Mondor (AP-HP) and Hôpital Intercommunal de Créteil, France and 6Service d'Histologie, Groupe Hospitalier Pitié-Salpétrière (AP-HP), Paris, France Offprint requests to: Stéphane Bretagne, Laboratoire de Parasitologie-Mycologie, Hôpital Henri Mondor, 51 avenue du Général DeLattre de Tassigny, 94010, Créteil, Cedex, France. Fax: 33 (0)1 49 81 36 01. e-mail: bretagne@univ-paris12.fr
Summary. The role of the airway epithelium in the development
of invasive aspergillosis in immunocompromised hosts has rarely
been studied although patients at risk for this infection frequently
have epithelial damage. We developed an in vitro model of primary
culture of human nasal epithelial cells (HNEC) in air-liquid interface,
which allows epithelial cell differentiation and mimics in vivo
airway epithelium. We subsequently tested 7-day and 24-hour Aspergillus
fumigatus filtrates on the apical side of HNEC to know whether
A. fumigatus, the main species responsible for invasive
aspergillosis, produces specific damage to the epithelial cells.
The results were compared with those obtained with non-pathogenic
filamentous fungi. Seven-day culture filtrates of A. fumigatus
and Penicillium chrysogenum induced electrophysiological
modifications whatever the fungus tested. In contrast, only 24-hour
A. fumigatus filtrates induced a specific decrease in transepithelial
resistance, hyperpolarization of the epithelium, and cytoplasmic
vacuolization of HNEC compared with both A. niger and Penicillium
chrysogenum. The inhibition of the A. fumigatus effects
with amiloride suggests that the 24-hour fungal filtrate acts
through sodium channels of HNEC. These early modifications of
the epithelial cells could facilitate colonization of the airways
by A. fumigatus. To know whether the molecules involved
are specific to A. fumigatus or simply produced more rapidly
than by other filamentous fungi warrants further investigation.
In this perspective, the primary culture of HNEC represents a
suitable model to study the interactions between airway epithelial
cells and A. fumigatus. Histol. Histopathol. 17, 1095-1101
(2002) |