TY - JOUR
T1 - Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia
AU - Glöckner, Michael
AU - Marwitz, Sebastian
AU - Rohmann, Kristina
AU - Watz, Henrik
AU - Nitschkowski, Dörte
AU - Rupp, Jan
AU - Dalhoff, Klaus
AU - Goldmann, Thorsten
AU - Drömann, Daniel
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Deutsche Forschungsgemeinschaft of TG and DD (247915558). The funding body was not involved in any experimental decisions, work, conclusions drawn or the draft of the manuscript. In addition, this work was supported by the German Center for Lung Research (DZL) and the University of Lübeck.
Funding Information:
The authors thank B F?ssel, T Tietz, U Knuppertz and J Hofmeister for their technical assistance. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Deutsche Forschungsgemeinschaft of TG and DD (247915558). The funding body was not involved in any experimental decisions, work, conclusions drawn or the draft of the manuscript. In addition, this work was supported by the German Center for Lung Research (DZL) and the University of L?beck.
Publisher Copyright:
© The Author(s) 2021.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.
AB - Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.
UR - http://www.scopus.com/inward/record.url?scp=85101929854&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/9b5aa658-c397-371d-b489-fbb5f9eb4180/
U2 - 10.1177/1753425921994906
DO - 10.1177/1753425921994906
M3 - Journal articles
C2 - 33646896
AN - SCOPUS:85101929854
SN - 1753-4259
VL - 27
SP - 251
EP - 259
JO - Innate Immunity
JF - Innate Immunity
IS - 3
ER -
