1. Immunology and Inflammation
  2. Microbiology and Infectious Disease

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

  1. Kathrin Tomasek  Is a corresponding author
  2. Alexander Leithner
  3. Ivana Glatzova
  4. Michael Sebastian Lukesch
  5. Calin C Guet  Is a corresponding author
  6. Michael Sixt  Is a corresponding author
  1. Institute of Science and Technology Austria, Austria
  2. VALANX Biotech GmbH, Austria
https://doi.org/10.7554/eLife.78995
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  1. Kathrin Tomasek
  2. Alexander Leithner
  3. Ivana Glatzova
  4. Michael Sebastian Lukesch
  5. Calin C Guet
  6. Michael Sixt
(2022)
Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
eLife 11:e78995.
https://doi.org/10.7554/eLife.78995
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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 mouse dendritic cells as a 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 the pathogenic strain CFT073 to CD14 reduced dendritic cell migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT pathway, both rate-limiting factors of T cell activation. This response was binary at the single cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. 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.

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All data are included in the manuscript. Source data are uploaded with this manuscript.

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Author details

  1. Kathrin Tomasek

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    kathrin.tomasek@epfl.ch
    Competing interests
    Kathrin Tomasek, is an inventor on patent application 21170193.3 (Methods determining the potential of drug for treating bacterial infections and composition for treating bacterial infections").".

  2. Alexander Leithner

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    No competing interests declared.

  3. Ivana Glatzova

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    No competing interests declared.

  4. Michael Sebastian Lukesch

    VALANX Biotech GmbH, Klosterneuburg, Austria
    Competing interests
    Michael Sebastian Lukesch, is affiliated with VALANX Biotech GmbH. The author has no financial interests to declare.Is an inventor on patent application 21170193.3 (Methods determining the potential of drug for treating bacterial infections and composition for treating bacterial infections").".

  5. Calin C Guet

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    calin.guet@ist.ac.at
    Competing interests
    Calin C Guet, is an inventor on patent application 21170193.3 (Methods determining the potential of drug for treating bacterial infections and composition for treating bacterial infections").".
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6220-2052

  6. Michael Sixt

    Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    sixt@ist.ac.at
    Competing interests
    Michael Sixt, is an inventor on patent application 21170193.3 (Methods determining the potential of drug for treating bacterial infections and composition for treating bacterial infections").".
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6620-9179

Funding

European Research Council (CoG 724373)

  • Michael Sixt

Austrian Science Fund (FWF P29911)

  • Michael Sixt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments are in accordance with the Austrian law for animal experiments. Permission was granted by the Austrian Federal Ministry of Science, Research and Economy (identification code: BMWFW 66.018/0010-WF/V/3b/2016). Mice were bred and maintained at the local animal facility in accordance IST Austria Ethical Committee or purchased from Charles River and maintained at the local animal facility in accordance with IST Austria Ethical Committee.

Reviewing Editor

  1. Ivan Zanoni, Harvard Medical School, United States

Version history

  1. Preprint posted: October 18, 2021 (view preprint)
  2. Received: March 26, 2022
  3. Accepted: July 19, 2022
  4. Accepted Manuscript published: July 26, 2022 (version 1)
  5. Version of Record published: August 8, 2022 (version 2)

Copyright

© 2022, Tomasek et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kathrin Tomasek
  2. Alexander Leithner
  3. Ivana Glatzova
  4. Michael Sebastian Lukesch
  5. Calin C Guet
  6. Michael Sixt
(2022)
Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14
eLife 11:e78995.
https://doi.org/10.7554/eLife.78995

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