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

Taufiqur R Bhuiyan,Taher Uddin,Anna Lundgren,Samuel B Lundin,Mohiul I Chowdhury,Firdausi Qadri,Jenni Adamsson,M M Towhidul Islam,Anders Janzon,Gernot Zissel

doi:10.1371/journal.pone.0093943

Taufiqur R Bhuiyan, Taher Uddin + Show 8 more

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https://doi.org/10.1371/journal.pone.0093943

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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.

Highlights

Helicobacter pylori infects the gastric mucosa and causes gastritis in the majority of infected individuals
Cytokine expression in gastric mucosa To determine if the mucosal immune response in Bangladeshi individuals is characterized by expression of both IL-17 and IFNc, as previously reported from studies from other parts of the world [9,10,11,17,20], the expression of IL-17 and IFN-c mRNA was analyzed in gastric biopsies collected from Bangladeshi adults (Figure 1)
Since it is difficult to get access to biopsy material from uninfected Bangladeshi participants as a consequence of the high prevalence of H. pylori infection in this population, we mainly used biopsies from uninfected and infected Swedes for comparison. We found that both IL-17 and IFN-c was expressed in the gastric mucosa of H. pylori infected Bangladeshi individuals and that the levels were comparable to those detected in gastric mucosa of infected Swedish participants

Summary

Introduction

Helicobacter pylori infects the gastric mucosa and causes gastritis in the majority of infected individuals. Evidence suggests that the chronic inflammation is dependent on T cells, since H. pylori infection causes little inflammation in T cell deficient mice [4]. The T cell response to H. pylori is dominated by CD4+ helper T cells [2,3,5]. Many studies demonstrate that these cells produce IFN-c and that the response is of a Th1 type [2,5,6,7]. More recently, the importance of IL-17 producing Th17 T cells for mucosal immunity has become increasingly clear [8] and recent studies suggest that these cells play an important role during H. pylori infection [2,9,10,11,12,13]

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