Borrelia burgdorferi modulates the physical forces and immunity signaling in endothelial cells
Raúl Aparicio Yuste,
Marie Muenkel,
Konstantinos Axarlis,
María J. Gómez Benito,
Annalena Reuss,
Grace Blacker,
Michal Caspi Tal,
Peter Kraiczy,
Effie E. Bastounis
Affiliations
Raúl Aparicio Yuste
Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Eberhard Karls University of Tübingen, Auf der Morgenstelle 28/E7, Tübingen 72076, Germany; Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain
Marie Muenkel
Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Eberhard Karls University of Tübingen, Auf der Morgenstelle 28/E7, Tübingen 72076, Germany
Konstantinos Axarlis
Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Eberhard Karls University of Tübingen, Auf der Morgenstelle 28/E7, Tübingen 72076, Germany
María J. Gómez Benito
Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain
Annalena Reuss
Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Eberhard Karls University of Tübingen, Auf der Morgenstelle 28/E7, Tübingen 72076, Germany
Grace Blacker
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA
Michal Caspi Tal
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
Peter Kraiczy
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
Effie E. Bastounis
Interfaculty Institute of Microbiology and Infection Medicine, Cluster of Excellence “Controlling Microbes to Fight Infections” (CMFI, EXC 2124), Eberhard Karls University of Tübingen, Auf der Morgenstelle 28/E7, Tübingen 72076, Germany; Corresponding author
Summary: Borrelia burgdorferi (Bb), a vector-borne bacterial pathogen and the causative agent of Lyme disease, can spread to distant tissues in the human host by traveling in and through monolayers of endothelial cells (ECs) lining the vasculature. To examine whether Bb alters the physical forces of ECs to promote its dissemination, we exposed ECs to Bb and observed a sharp and transient increase in EC traction and intercellular forces, followed by a prolonged decrease in EC motility and physical forces. All variables returned to baseline at 24 h after exposure. RNA sequencing analysis revealed an upregulation of innate immune signaling pathways during early but not late Bb exposure. Exposure of ECs to heat-inactivated Bb recapitulated only the early weakening of EC mechanotransduction. The differential responses to live versus heat-inactivated Bb indicate a tight interplay between innate immune signaling and physical forces in host ECs and suggest their active modulation by Bb.
