The effect of a helicobacter pylori lysate on the tolerant state of human monocyte derived dendritic cells
2014
The worldwide observed change in the commensal flora is thought to affect tolerance to allergens and other harmless antigens. Epidemiological studies suggest that infection with H. pylori protects against developing asthma. Symptoms of allergic airway inflammation were reduced in mice infected with H. pylori and this effect has been linked to the modulation of dendritic cell (DC) function, induction of regulatory T cells (Treg) and production of IL-10 (Arnold, I.C. et al. JCI 2011 and Oertli, M. et al. JCI 2012). As live infection with H. pylori is potentially harmful, we tested a lysate of H. pylori on human monocyte-derived (mo-)DC. In this in vitro culture system DCs exposed to H. pylori lysate in presence or absence of LPS for 48 h fully matured, but strongly increased release of the anti-inflammatory cytokine IL-10. Subsequently, DC exposed to the lysate were cultured with naive T cells. Th1 cell skewing by DCs stimulated with the lysate was reduced. In contrast, T cells differentiated by the lysate-exposed DCs of a subgroup of donors secreted more IL-10 compared to T cells from control LPS-primed DCs, suggesting the induction of Tregs. These Tregs were able to suppress proliferation of alloreactive memory T cells in vitro . Our results suggest that H. pylori lysate has strong IL-10 inducing capacities also in human mo-DCs, which can induce IL-10 secreting T cells with a suppressive function. Therefore we provide evidence that lysate from H. pylori, comparable to live bacteria , induces a tolerant state of the immune system. As this approach is not associated with the drawback of live infection the potential usage as a therapeutic approach needs to be further determined.
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