Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults

PLoS One. 2014 Apr 8;9(4):e93943. doi: 10.1371/journal.pone.0093943. eCollection 2014.

Abstract

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-γ 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-γ 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-γ after MP stimulation, but little Th2 cytokines. IL-17 and IFN-γ 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-γ, compared to adult cells after MP stimulation. In contrast, polyclonal stimulation induced lower levels IL-17 and IFN-γ 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-1β 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-γ in response to Hp from an early age and indicate a potential role for IL-1β in promoting Th17 responses to Hp during infancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bangladesh
  • Child, Preschool
  • Female
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / immunology*
  • Humans
  • Infant
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Sweden
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology
  • Young Adult

Substances

  • Interleukin-17
  • Interferon-gamma

Grants and funding

This work was supported by the Swedish Agency for Research and Economic Cooperation (SAREC) (grant INT-ICDDR,B-HN-01-AV), the Marianne and Markus Wallenberg Foundation through the support to GUVAX as well as the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.