Th1 and Th17 Responses to Helicobacter pylori in Bangladeshi Infants, Children and Adults

Both Th1 and Th17 cells are important components of the immune response to Helicobacter pylori (Hp) in adults, but less is known about T cell responses to Hp during early childhood, when the infection is often acquired. We investigated Th1 and Th17 type responses to Hp in adults, children and infants in Bangladesh, where Hp is highly endemic. IL-17 and IFN-gamma mRNA levels in gastric biopsies from Hp-infected Bangladeshi adults were analyzed and compared to levels in infected and uninfected Swedish controls. Since biopsies could not be collected from infants and children, cytokine responses in Bangladeshi infants (6-12 months), children (3-5 years) and adults (> 19 years) were instead compared by stimulating peripheral blood mononuclear cells (PBMCs) with a Hp membrane preparation (MP) and analyzing culture supernatants by ELISA and cytometric bead array. We found significantly higher expression of IL-17 and IFN-gamma mRNA in gastric mucosa of Hp-infected Bangladeshi and Swedish adults compared to uninfected Swedish controls. PBMCs from all age groups produced IL-17 and IFN-gamma after MP stimulation, but little Th2 cytokines. IL-17 and IFN-gamma were primarily produced by CD4(+) T cells, since CD4(+) T cell depleted PBMCs produced reduced amounts of these cytokines. Infant cells produced significantly more IL-17, but similar levels of IFN-gamma, compared to adult cells after MP stimulation. In contrast, polyclonal stimulation induced lower levels IL-17 and IFN-gamma in infant compared to adult PBMCs and CD4(+) T cells. The strong IL-17 production in infants after MP stimulation was paralleled by significantly higher production of the IL-17 promoting cytokine IL-1 beta from infant compared to adult PBMCs and monocytes. In conclusion, these results show that T cells can produce high levels of IL-17 and IFN-gamma in response to Hp from an early age and indicate a potential role for IL-1 beta in promoting Th17 responses to Hp during infancy.