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

doi:10.1016/j.isci.2022.104793

Borrelia burgdorferi modulates the physical forces and immunity signaling in endothelial cells

iScience. 2022 Jul 20;25(8):104793. doi: 10.1016/j.isci.2022.104793. eCollection 2022 Aug 19.

Authors

Affiliations

¹ 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.
² Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain.
³ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.

Abstract

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.

Keywords: Biophysics; Cell biology; Immunology; Microbiology; Transcriptomics.