Role of NOD1 and ALPK1/TIFA signalling in innate immunity against helicobacter pylori infection

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Abstract

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.

Original languageEnglish
Title of host publicationMolecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori
EditorsSteffen Backer
Place of PublicationSwitzerland
PublisherSpringer
Pages159-177
Number of pages19
ISBN (Electronic)9783030151386
ISBN (Print)9783030151379
DOIs
Publication statusPublished - 24 May 2019

Publication series

NameCurrent Topics in Microbiology and Immunology
Volume421
ISSN (Print)0070-217X
ISSN (Electronic)2196-9965

Keywords

  • ALPK1
  • cagPAI
  • NOD1
  • Peptidoglycan
  • TIFA

Cite this

Ying, L., & Ferrero, R. L. (2019). Role of NOD1 and ALPK1/TIFA signalling in innate immunity against helicobacter pylori infection. In S. Backer (Ed.), Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori (pp. 159-177). (Current Topics in Microbiology and Immunology; Vol. 421). Switzerland: Springer. https://doi.org/10.1007/978-3-030-15138-6_7