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Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14

View ORCID ProfileKathrin Tomasek, Alexander Leithner, Ivana Glatzova, Michael S. Lukesch, View ORCID ProfileCălin C. Guet, View ORCID ProfileMichael Sixt
doi: https://doi.org/10.1101/2021.10.18.464770
Kathrin Tomasek
1Institute of Science and Technology, IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • For correspondence: kathrin.tomasek@gmail.com michael.sixt@ist.ac.at calin@ist.ac.at
Alexander Leithner
1Institute of Science and Technology, IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria
2Kennedy Institute of Rheumatology, University of Oxford, United Kingdom
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Ivana Glatzova
1Institute of Science and Technology, IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria
3University of Copenhagen, Denmark
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Michael S. Lukesch
4VALANX Biotech GmbH, Plöcking 1, 3400 Klosterneuburg, Austria
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Călin C. Guet
1Institute of Science and Technology, IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • For correspondence: kathrin.tomasek@gmail.com michael.sixt@ist.ac.at calin@ist.ac.at
Michael Sixt
1Institute of Science and Technology, IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Michael Sixt
  • For correspondence: kathrin.tomasek@gmail.com michael.sixt@ist.ac.at calin@ist.ac.at
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Abstract

A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 18, 2021.
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Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
Kathrin Tomasek, Alexander Leithner, Ivana Glatzova, Michael S. Lukesch, Călin C. Guet, Michael Sixt
bioRxiv 2021.10.18.464770; doi: https://doi.org/10.1101/2021.10.18.464770
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Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
Kathrin Tomasek, Alexander Leithner, Ivana Glatzova, Michael S. Lukesch, Călin C. Guet, Michael Sixt
bioRxiv 2021.10.18.464770; doi: https://doi.org/10.1101/2021.10.18.464770

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