Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes

Figures & data

Figure 1 The effect of gastritis pattern on gastric acid production and associations with duodenal and gastric disease.

Table 1 Major virulence factors and their effects on inflammation and the immune response

Virulence factor	Pro-inflammatory roles	Anti-inflammatory roles
CagA and the cagPAI-encoded type IV secretion system	Stimulates NF-κB activation in gastric epithelial cells, leading to expression of pro-inflammatory cytokines and chemokines; activation of MAPK signaling, leading to cell proliferation and inflammatory gene expression; disruption of epithelial cell junctions	CagA induces cell cycle arrest in T-cells; cagPAI-mediated signaling downregulates the expression of pro-inflammatory hBD1
VacA	Induction or dysregulation of autophagy; induces IL-8 production by monocytes and macrophages via p38 MAPK signaling; activates mast cells and induces inflammatory cytokine expression; plays a role in maintaining colonization	Binds CD18 on human T-cells and directly inhibits the activation and proliferation of human B and T lymphocytes; exerts tolerizing effects on DCs to stimulate a Treg response; inhibits antigen presentation; inhibits DC maturation via effects on E2F1 signaling; induces T-cells to express the Treg transcription factor Foxp3
DupA and the tfs4-encoded type IV secretion system	Induction of pro-inflammatory cytokine secretion by monocytes and epithelial cells	None reported
HP-NAP	Activates neutrophils and induces ROS; stimulates TLR2; stimulates macrophages to produce IL-12 and IL-23; induces IL-6 production by mast cells; inhibits Th2 responses and promotes the development of a Th1 response	None reported
Heat shock protein 60	Interacts with TLR2; stimulates macrophages and induces IL-12 and IL-23 expression	Induces a strong IL-10 response from human peripheral blood mononuclear cells
OipA	Mediates closer interaction with gastric epithelium and induces pro-inflammatory cytokine expression; reduces IL-10 production by DCs; disruption of epithelial cell tight junctions (with cagPAI signaling)	Inhibits DC maturation and promotes the differentiation of naïve T-cells into Tregs IL-6; modulation of Th1/Th2 balance
Peptidyl prolyl cis-, transisomerase (HP0175)	Interacts with TLR4; stimulates a Th17 response	None reported
Fucosylated Lewis blood group antigens (LPS moieties)	Interact with major adhesins; mediate closer interaction and exposure of epithelial cells to H. pylori virulence factors	Interaction with DC-SIGN on DCs to increase IL-10 expression and suppress
SabA	Interacts with sialylated receptors on neutrophils to induce ROS production; mediates closer interaction and exposure of epithelial cells to H. pylori virulence factors	None reported
Gamma-glutamyl transpeptidase	Induces NF-κB activation, IL-8 production, and ROS by gastric epithelial cells; gastric epithelial cell death; stimulates a Th17 response	Potent T-cell suppressant activity; induces T-cells to express the Treg transcription factor Foxp3; upregulates COX2 expression in T-cells which modulates Th1 response

Abbreviations: IL, interleukin; DC, dendritic cell; H. pylori, Helicobacter pylori; ROS, reactive oxygen species; TLR, toll-like receptor; Th, T-helper; LPS, lipopolysaccharide; NAP, neutrophil-activating protein.