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T4SS-dependent TLR5 activation by Helicobacter pylori infection

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Listed:
  • Suneesh Kumar Pachathundikandi

    (Friedrich Alexander University Erlangen-Nuremberg)

  • Nicole Tegtmeyer

    (Friedrich Alexander University Erlangen-Nuremberg)

  • Isabelle Catherine Arnold

    (University of Zurich)

  • Judith Lind

    (Friedrich Alexander University Erlangen-Nuremberg)

  • Matthias Neddermann

    (Friedrich Alexander University Erlangen-Nuremberg)

  • Christina Falkeis-Veits

    (Institute for Pathology, Klinikum Bayreuth)

  • Sujay Chattopadhyay

    (JIS University)

  • Mark Brönstrup

    (Helmholtz Centre for Infection Research)

  • Werner Tegge

    (Helmholtz Centre for Infection Research)

  • Minsun Hong

    (Yonsei University)

  • Heinrich Sticht

    (Friedrich Alexander University Erlangen-Nuremberg)

  • Michael Vieth

    (Institute for Pathology, Klinikum Bayreuth)

  • Anne Müller

    (University of Zurich)

  • Steffen Backert

    (Friedrich Alexander University Erlangen-Nuremberg)

Abstract

Toll-like receptor TLR5 recognizes a conserved domain, termed D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Highly virulent H. pylori strains possess a type IV secretion system (T4SS) for delivery of virulence factors into gastric epithelial cells. Here, we show that one of the H. pylori T4SS components, protein CagL, can act as a flagellin-independent TLR5 activator. CagL contains a D1-like motif that mediates adherence to TLR5+ epithelial cells, TLR5 activation, and downstream signaling in vitro. TLR5 expression is associated with H. pylori infection and gastric lesions in human biopsies. Using Tlr5-knockout and wild-type mice, we show that TLR5 is important for efficient control of H. pylori infection. Our results indicate that CagL, by activating TLR5, may modulate immune responses to H. pylori.

Suggested Citation

  • Suneesh Kumar Pachathundikandi & Nicole Tegtmeyer & Isabelle Catherine Arnold & Judith Lind & Matthias Neddermann & Christina Falkeis-Veits & Sujay Chattopadhyay & Mark Brönstrup & Werner Tegge & Mins, 2019. "T4SS-dependent TLR5 activation by Helicobacter pylori infection," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13506-6
    DOI: 10.1038/s41467-019-13506-6
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