Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity

Abstract

During Helicobacter pylori (Hp) infections, innate immune cells may be positively or negatively modulated by Hp compounds or by Hp-induced cytokines. We have shown previously that the natural cytotoxic activity of PBMC was lower in Hp-infected [Hp(+)] than Hp-uninfected individuals [Hp(-)]. Here, we asked whether the Hp-modulated cytotoxic amplitude is associated with changes in the number of NK cells, their activation or intracellular cytokine expression. Flow cytometry immunophenotyping of PBMC was performed with regard to the surface receptors CD3, CD56 and CD25, and intracellular cytokine expression of IL-2, IFN-γ and IL-10 after in vitro stimulation with Hp glycine acid extract (GE), Hp LPS or standard Escherichia coli LPS. Hp GE-driven enhancement of lymphocyte cytotoxic activity was associated with the expansion of CD3(-)CD56(+)CD25(+) NK cells and the up-regulation of IFN-γ and/or IL-2 synthesis, up to the higher level in Hp(-) than in Hp(+), while Hp LPS-mediated decrease in lymphocyte cytotoxicity was accompanied by the lack of CD3(-)CD56(+)CD25(+) NK propagation, the inhibition of pro-inflammatory cytokine expression and intense expansion of IL-10-producing NK cells. Thus, the cytotoxic and cytokine activities of NK cells were dependent on the type of antigenic challenge and the Hp status, that is, NK cells could be modulated positively by Hp GE Ags and negatively by Hp LPS.

Impact ofHelicobacter pylorion the healing process of the gastric barrier

“…However, it has been shown that H. pylori LPS is able to downregulate the lymphocyte blastogenic response, probably due to the interference with the process of macrophage maturation[46-48,94]. It also downregulates the phagocytic potential of macrophages[44] and decreases the cytotoxic activity of NK cells[45,68]. In the gastric epithelium, colonized by pathogenic microorganisms, including H. pylori , probably IL-33 acting as an alarming molecule can induce the signalling beneficial for tissue recovery due to a short-term increase in endothelial permeability.…”

“…This is by reducing the host immune response mechanisms including phagocytosis[44], Natural Killer cells activity[45] and proliferation of T lymphocytes[46-48]. LPS through binding with dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) may interfere with the development of specific immune response[49,50].…”

Host pathogen interactions in Helicobacter pylori related gastric cancer

“…The primary host immune response mechanisms, such as phagocytosis and natural killer (NK) cell activity, have been found to be downregulated by H. pylori LPS[17,18,39,40]. Adaptive immunity is also targeted by H. pylori compounds[1,15,41,42].…”

Molecular mimicry inHelicobacter pyloriinfections

“…Previous studies showed that H. pylori LPS possesses immunomodulatory properties that diminish the effectiveness of the phagocytosis, cytotoxic activity and the expansion of NK cells and T lymphocytes[40-42]. …”