T4SS-dependent TLR5 activation by Helicobacter pylori infection.

Pachathundikandi SK; Tegtmeyer N; Arnold IC; Lind J; Neddermann M; Falkeis-Veits C; Chattopadhyay S; Brönstrup M; Tegge W; Hong M; Sticht H; Vieth M; Müller A; Backert S

doi:10.1038/s41467-019-13506-6

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Journal article

T4SS-dependent TLR5 activation by Helicobacter pylori infection.

Pachathundikandi SK Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Tegtmeyer N Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Arnold IC Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Lind J Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Neddermann M Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Falkeis-Veits C Institute for Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Chattopadhyay S JIS Institute of Advanced Studies and Research, JIS University, Kolkata, 700091, India.
Brönstrup M Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Tegge W Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Hong M Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Sticht H Institute of Biochemistry, Division of Bioinformatics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Vieth M Institute for Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Müller A Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Backert S Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany. Steffen.Backert@fau.de.

2019-12-18

Published in:

Nature communications. - 2019

English 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.

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