Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

Michael Glöckner; Sebastian Marwitz; Kristina Rohmann; Henrik Watz; Dörte Nitschkowski; Jan Rupp; Klaus Dalhoff; Thorsten Goldmann; Daniel Drömann

doi:10.1177/1753425921994906

Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

Michael Glöckner^*, Sebastian Marwitz, Kristina Rohmann, Henrik Watz, Dörte Nitschkowski, Jan Rupp, Klaus Dalhoff, Thorsten Goldmann, Daniel Drömann

^*Corresponding author for this work

3 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Innate Immunity
Volume	27
Issue number	3
Pages (from-to)	251-259
Number of pages	9
ISSN	1753-4259
DOIs	https://doi.org/10.1177/1753425921994906
Publication status	Published - 04.2021

Funding

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. 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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10.1177/1753425921994906

Cite this

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title = "Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia",

abstract = "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.",

author = "Michael Gl{\"o}ckner and Sebastian Marwitz and Kristina Rohmann and Henrik Watz and D{\"o}rte Nitschkowski and Jan Rupp and Klaus Dalhoff and Thorsten Goldmann and Daniel Dr{\"o}mann",

note = "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 L{\"u}beck. 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: {\textcopyright} The Author(s) 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = apr,

doi = "10.1177/1753425921994906",

language = "English",

volume = "27",

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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.

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ER -

Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

Abstract

Funding

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