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ALPK1 and TIFA Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System

48 Pages Posted: 12 Apr 2018 Sneak Peek Status: Published

See all articles by Stephanie Zimmermann

Stephanie Zimmermann

Max Planck Institute for Infection Biology - Department of Molecular Biology

Lennart Pfannkuch

Max Planck Institute for Infection Biology - Department of Molecular Biology

Munir A. Al-Zeer

Max Planck Institute for Infection Biology - Department of Molecular Biology

Sina Bartfeld

Max Planck Institute for Infection Biology - Department of Molecular Biology

Manuel Koch

Max Planck Institute for Infection Biology - Department of Molecular Biology

Jianping Liu

Max Planck Institute for Infection Biology - Department of Molecular Biology

Cindy Rechner

Max Planck Institute for Infection Biology - Department of Molecular Biology

Meike Soerensen

Max Planck Institute for Infection Biology - Department of Molecular Biology

Olga Sokolova

Otto-von-Guericke-Universität Magdeburg - Institute of Experimental Internal Medicine

Alla Zamyatina

Universität für Bodenkultur Wien (BOKU) - Department of Chemistry

Paul Kosma

Universität für Bodenkultur Wien (BOKU) - Department of Chemistry

André P. Mäurer

Max Planck Institute for Infection Biology - Department of Molecular Biology

Frithjof Glowinski

Max Planck Institute for Infection Biology - Department of Molecular Biology

Klaus-Peter Pleissner

Max Planck Institute for Infection Biology - Department of Molecular Biology

Monika Schmid

Max Planck Institute for Infection Biology - Department of Molecular Biology

Volker Brinkmann

Max Planck Institute for Infection Biology - Department of Molecular Biology

Michael Naumann

Otto-von-Guericke-Universität Magdeburg - Institute of Experimental Internal Medicine

Marion Rother

Steinbeis Innovation, Center for Systems Biomedicine

Nikolaus Machuy

Max Planck Institute for Infection Biology - Department of Molecular Biology

Thomas F. Meyer

Max Planck Institute for Infection Biology - Department of Molecular Biology

More...

Abstract

Activation of transcription factor NF-κB is a hallmark of infection with the gastric pathogen Helicobacter pylori and associated with inflammation and carcinogenesis. Genome-wide RNAi screening revealed numerous hits involved in H. pylori-, but not IL-1β- and TNF-α- dependent NF-κB regulation. Pathway analysis including CRISPR/Cas9-knockout and recombinant protein technology, immunofluorescence microscopy, immunoblotting, mass spectrometry and mutant H. pylori strains, identified the H. pylori metabolite D-glycero-β-D-manno-heptose 1,7-bisphosphate (βHBP) as a cagPAI type IV secretion system (T4SS)-dependent effector of NF-κB activation in infected cells. Upon pathogen-host cell contact, TIFA forms large complexes (TIFAsomes) including interacting host factors, such as TRAF2. NF-κB activation, TIFA phosphorylation as well as TIFAsome formation depended on a functional ALPK1 kinase, highlighting the ALPK1-TIFA axis as core of a novel innate immune pathway. ALPK1-TIFA-mediated NF-κB activation was independent of CagA protein translocation, indicating that CagA translocation and HBP delivery to host cells are distinct features of the pathogen's T4SS.

Suggested Citation

Zimmermann, Stephanie and Pfannkuch, Lennart and A. Al-Zeer, Munir and Bartfeld, Sina and Koch, Manuel and Liu, Jianping and Rechner, Cindy and Soerensen, Meike and Sokolova, Olga and Zamyatina, Alla and Kosma, Paul and Mäurer, André P. and Glowinski, Frithjof and Pleissner, Klaus-Peter and Schmid, Monika and Brinkmann, Volker and Naumann, Michael and Rother, Marion and Machuy, Nikolaus and Meyer, Thomas F., ALPK1 and TIFA Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System (2018). Available at SSRN: https://ssrn.com/abstract=3155755 or http://dx.doi.org/10.2139/ssrn.3155755
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Stephanie Zimmermann

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Lennart Pfannkuch

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Munir A. Al-Zeer

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Sina Bartfeld

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Manuel Koch

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Jianping Liu

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Cindy Rechner

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Meike Soerensen

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Olga Sokolova

Otto-von-Guericke-Universität Magdeburg - Institute of Experimental Internal Medicine

Magdeburg, 39120
Germany

Alla Zamyatina

Universität für Bodenkultur Wien (BOKU) - Department of Chemistry

1190 Vienna
Austria

Paul Kosma

Universität für Bodenkultur Wien (BOKU) - Department of Chemistry

1190 Vienna
Austria

André P. Mäurer

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Frithjof Glowinski

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Klaus-Peter Pleissner

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Monika Schmid

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Volker Brinkmann

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Michael Naumann

Otto-von-Guericke-Universität Magdeburg - Institute of Experimental Internal Medicine

Magdeburg, 39120
Germany

Marion Rother

Steinbeis Innovation, Center for Systems Biomedicine

14612 Berlin-Falkensee
Germany

Nikolaus Machuy

Max Planck Institute for Infection Biology - Department of Molecular Biology

Virchowweg 12
10117 Berlin
Germany

Thomas F. Meyer (Contact Author)

Max Planck Institute for Infection Biology - Department of Molecular Biology ( email )

Virchowweg 12
10117 Berlin
Germany

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