Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function.
Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6-12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases.
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.|Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Robert J
RJ
Lee
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Alan D
AD
Workman
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Ryan M
RM
Carey
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Bei
B
Chen
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Phillip L
PL
Rosen
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Laurel
L
Doghramji
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Nithin D
ND
Adappa
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
James N
JN
Palmer
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
David W
DW
Kennedy
Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.|Philadelphia VA Medical Center Surgical Services, Philadelphia, Pennsylvania, USA.|Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
Noam A
NA
Cohen
D000348:Aflatoxins / Q000737:chemistry / Q000633:toxicity*; D001230:Aspergillus / Q000737:chemistry*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002923:Cilia / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010256:Paranasal Sinuses / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology
D000348:Aflatoxins