Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection

  • Le Ying
  • Richard L. FerreroEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 421)


The human pathogen Helicobacter pylori interacts intimately with gastric epithelial cells to induce inflammatory responses that are a hallmark of the infection. This inflammation is a critical precursor to the development of peptic ulcer disease and gastric cancer. A major driver of this inflammation is a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI), present in a subpopulation of more virulent H. pylori strains. The cagPAI T4SS specifically activates signalling pathways in gastric epithelial cells that converge on the transcription factor, nuclear factor-κB (NF-κB), which in turn upregulates key immune and inflammatory genes, resulting in various host responses. It is now clear that H. pylori possesses several mechanisms to activate NF-κB in gastric epithelial cells and, moreover, that multiple signalling pathways are involved in these responses. Two of the dominant signalling pathways implicated in NF-κB-dependent responses in epithelial cells are nucleotide-binding oligomerisation domain 1 (NOD1) and a newly described pathway involving alpha-kinase 1 (ALPK1) and tumour necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA). Although the relative roles of these two pathways in regulating NF-κB-dependent responses still need to be clearly defined, it is likely that they work cooperatively and non-redundantly. This chapter will give an overview of the various mechanisms and pathways involved in H. pylori induction of NF-κB-dependent responses in gastric epithelial cells, including a ′state-of-the-art′ review on the respective roles of NOD1 and ALPK1/TIFA pathways in these responses.


NOD1 TIFA ALPK1 Peptidoglycan cagPAI 



The authors thank Christian Ferrero for the preparation of Fig. 1. Research in RLF’s laboratory is supported by a project grant (APP1107930) and a Senior Research Fellowship (APP1079904) from the National Health and Medical Research Council of Australia. Dr. L. Ying’s position is supported by funding from the U. S. Department of Defense (Award No. W81XWH-17-1-0606). Research at the Hudson Institute of Medical Research is supported by the Victorian Government’s Operational Infrastructure Support Program.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical ResearchMonash UniversityClaytonAustralia
  2. 2.Department of Molecular and Translational MedicineMonash UniversityClaytonAustralia
  3. 3.Department of Microbiology, Biomedicine Discovery InstituteMonash UniversityClaytonAustralia

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