Innate immune activation and modulatory factors of Helicobacter pylori towards phagocytic and nonphagocytic cells

ElsevierVolume 82, June 2023, 102301Current Opinion in ImmunologyAuthor links open overlay panel, , ,

Helicobacter pylori is an intriguing obligate host-associated human pathogen with a specific host interaction biology, which has been shaped by thousands of years of host-pathogen coevolution. Molecular mechanisms of interaction of H. pylori with the local immune cells in the human system are less well defined than epithelial cell interactions, although various myeloid cells, including neutrophils and other phagocytes, are locally present or attracted to the sites of infection and interact with H. pylori. We have recently addressed the question of novel bacterial innate immune stimuli, including bacterial cell envelope metabolites, that can activate and modulate cell responses via the H. pylori Cag type IV secretion system. This review article gives an overview of what is currently known about the interaction modes and mechanisms of H. pylori with diverse human cell types, with a focus on bacterial metabolites and cells of the myeloid lineage including phagocytic and antigen-presenting cells.

Section snippetsHelicobacter pylori, its native niche in the stomach and its potential to contact various cell types of the epithelial, myeloid and lymphoid lineages

It is well established that the bacterium Helicobacter pylori is a chronic stomach pathogen of major global importance, since more than half of the world population carries this bacterial species in their stomachs [1]. Infected individuals usually show asymptomatic chronic gastritis, but some develop gastric ulcers and gastric cancer [2]. Disease progression seems, by association studies, to be determined by several key factors, among them host genetic predisposition, bacterial genotype, and

Interaction of H. pylori with gastric epithelial cells and concomitant innate immune activation and evasion

The molecular interaction of H. pylori with epithelial cells, primarily of gastric origin, has been very well studied in the past 20 years, also thanks to well-established human gastric cell lines. H. pylori activates gastric epithelial cells by different innate immune pathways upon intimate cell adherence 22, 23, 24, 25. Adherence of H. pylori is by outer membrane protein autotransporter adhesins. The best-characterized among them are SabA and BabA, which interact with cellular glycans,

Current knowledge on the influence of clretain-->H. pylori on cells of different myeloid lineages and antigen-presenting cells in vivo and clretain-->in vitro

In contrast to epithelial cells, the role of phagocytic cells during infection is commonly assigned to directly eliminate the pathogens locally and to translate the immediate danger signals to adaptive immune cells such as T-cells and antibody-producing B-cells. H. pylori, given the chronic nature of its infection in the human stomach, supposedly has evolved to evade mechanism of diverse phagocytes. But do we have sufficient evidence for this hypothesis? Macrophages, monocytes, immigrating

Variation of bacteria in immune-modulatory traits

H. pylori is one of the most variable pathogenic bacteria, displaying a unique genetic fingerprint in each strain [155] and even a strong intrapopulation diversification in one single patient stomach [156]. This led us to hypothesize that each strain effectuates a different cell-autonomous immune activation and even has possibilities to individually vary its interaction with human cells. This is an area where much remains to be discovered and we will not discuss here the individual variation on

Conclusions and outlook

We can safely conclude at this point in time already from the existing literature that H. pylori interacts in a specific and strain-specific manner with epithelial and phagocytic cells, including some overlap such as the importance of heptose metabolite transport and innate signaling. H. pylori also appears to use its CagT4SS for fine-tuning these interactions, strain-specifically, over time, and in all so-far characterized cell types, in particular in monocytes-macrophages and neutrophils. H.

Conflict of interest statement

The authors indicate no conflict of interest.

Acknowledgements

We are grateful for funding of our summarized and ongoing research in this area by the Center grant CRC 900 (German Research Foundation, DFG, Germany, project no. 158989968), in particular project B6 to CJ, the DFG single grant project JO 344/5-1 to CJ, and the German Center of Infection Research (DZIF), Germany, projects 06.809 and 06.820, to CJ. LF and MH were additionally supported by the graduate program “Infection Research on Human Pathogens at MvPI.” We thank all past and present lab

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