A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes.
The respiratory tract with its ease of access, vast surface area and dense network of antigen-presenting cells (APCs) represents an ideal target for immune-modulation. Bio-mimetic nanocarriers such as virosomes may provide immunomodulatory properties to treat diseases such as allergic asthma. In our study we employed a triple co-culture model of epithelial cells, macrophages and dendritic cells to simulate the human airway barrier. The epithelial cell line 16HBE was grown on inserts and supplemented with human blood monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs) for exposure to influenza virosomes and liposomes. Additionally, primary human nasal epithelial cells (PHNEC) and EpCAM+ epithelial progenitor cell mono-cultures were utilized to simulate epithelium from large and smaller airways, respectively. To assess particle uptake and phenotype change, cell cultures were analyzed by flow cytometry and pro-inflammatory cytokine concentrations were measured by ELISA. All cell types internalized virosomes more efficiently than liposomes in both mono- and co-cultures. APCs like MDMs and MDDCs showed the highest uptake capacity. Virosome and liposome treatment caused a moderate degree of activation in MDDCs from mono-cultures and induced an increased cytokine production in co-cultures. In epithelial cells, virosome uptake was increased compared to liposomes in both mono- and co-cultures with EpCAM+ epithelial progenitor cells showing highest uptake capacity. In conclusion, all cell types successfully internalized both nanocarriers with virosomes being taken up by a higher proportion of cells and at a higher rate inducing limited activation of MDDCs. Thus virosomes may represent ideal carrier antigen systems to modulate mucosal immune responses in the respiratory tract without causing excessive inflammatory changes.
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Rebecca A M
RA
Blom
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
Silvia T
ST
Erni
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
Kristína
K
Krempaská
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
Olivier
O
Schaerer
Institute of Anatomy, University of Zürich, Zürich, Switzerland.|Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
R Maarten
RM
van Dijk
Mymetics SA, Epalinges, Switzerland.
Mario
M
Amacker
Swiss Federal Institute of Intellectual Property, Bern, Switzerland.
Christian
C
Moser
Division of Thoracic Surgery, Bern University Hospital, University of Bern, Bern, Switzerland.|Department of Clinical Research, University of Bern, Bern, Switzerland.
Sean R R
SR
Hall
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
Christophe
C
von Garnier
Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
Fabian
F
Blank
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