Helicobacter pylori VacA Activates NF‐κB in T Cells via the Classical but not Alternative Pathway

Abstract

VacA has two paradoxical effects on T cells, immunosuppression, and proinflammatory effects. The latter is mediated by NF-kappaB activation.

Gene Expression Profiling in Gastric Mucosa from Helicobacter pylori-Infected and Uninfected Patients Undergoing Chronic Superficial Gastritis

“…LPS, cagA, vacA), but also by pro-apoptotic and necrotic stimuli (ROS, RNS) [70]–[72]. Several studies indicated that H. pylori -related gastric inflammation and cancer were associated with increased NF-κB activation [23], [67], [4], [13]. In the present study, NF-κB was an important central point in network 1(Figure 3).…”

“…Upon infection, H. pylori activates multiple intracellular pathways in epithelial cells, such as MAPK, NF-κB, Wnt/β-catenin, PI3K pathways and signal transducers [67]–[68], [4], [13]. The Wnt/Wingless signaling transduction pathway plays an important role in both embryonic development and tumorigenesis.…”

“…VacA secreted by type V-secretion system is internalized into host cells by endocytosis and influences different cellular processes, including cell vacuolation, mitochondria-dependent cell death and an increase in the permeability of gastric epithelium, inhibition of T-cell activation and proliferation, and initiation of proinflammatory response [3]. Besides, VacA also activate PI3A/Akt, MAPK and NF-κB signaling [3]–[4]. Neutrophil-activating protein (HP-NAP) secreted by H. pylori is also an important virulence factor due to its ability to induce neutrophils to produce reactive oxygen radicals [5].…”

Helicobacter pylori vacuolating toxin

“…Hisatsune et al [231] found that in U937 macrophage-like cells, VacA directly increases IL-8 production by activation of p38 via intracellular Ca 2+ release, leading to activation of the transcription factors ATF-2, cAMP response element binding (CREB) protein and nuclear transcription factor kappa B (NF-κB). VacA has been also reported to induce NF-κB in Jurkat T cells [232]. Thus, the toxin seems to exert two paradoxical activities on T cells (namely, immunosuppression and proinflammatory effects); the latter mediated by NF-κB activation.…”

The Versatility of the Helicobacter pylori Vacuolating Cytotoxin VacA in Signal Transduction and Molecular Crosstalk

“…In the latter study, VacA-induced p38 activation in U937 cells revealed a prominent role in stimulation IL-8 production via ATF-2, cAMP response element binding (CREB) protein and nuclear transcription factor kappa B (NF-κB). Interestingly, VacA can also induce NF-κB in T cells [106], thus the toxin obviously has two paradoxical activities on T cells, immunosuppression and pro-inflammatory effects (Figure 3J). In addition, in neutrophils and macrophages, VacA treatment can stimulate the expression of Cox-2 (cyclooxygenase-2), a pro-inflammatory enzyme [102].…”