Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori–infected children

Abstract

Helicobacter pylori induces less gastric inflammation in children than adults. Here we investigated whether this reduced inflammation involves dysregulated Th17 responses. H. pylori-infected children and adults in Santiago, Chile had similar levels of H. pylori colonization, proportions of bacteria containing cagA and s1/s2 vacA markers of virulence and strain genotypes (predominantly hpEurope), but the children had significantly reduced levels of gastric inflammation and neutrophil infiltration. The reduced neutrophil accumulation in infected children was accompanied by significantly fewer gastric Th17 cells and significantly lower levels of IL-17-specific mRNA and protein compared to infected adults. The gastric mucosa of H. pylori-infected children also contained higher numbers of IL-10+ cells and increased levels of both IL-10 and Foxp3 mRNA compared to that of infected adults. Thus, reduced gastric inflammation, including diminished neutrophil accumulation, in H. pylori-infected children compared with infected adults is likely due to down-regulated gastric Th17/IL-17 responses as a consequence of enhanced mucosal regulatory T cell activity in the children.

Cytokine BAFF Released byHelicobacter pylori–Infected Macrophages Triggers the Th17 Response in Human Chronic Gastritis

“…Many data support the idea that the Th17 response favors the bacterial growth in mice and contributes to the inflammation both in mice and in humans (3)(4)(5), although its role is probably not essential because IFN-g has the largest effect (2). Along with this evidence, other data suggest that this response may exert a regulatory effect rather than a proinflammatory one (6).…”

Role of childhood infection in the sequelae of H. pylori disease

“…12 The degree of gastric inflammation in children, however, is significantly less compared with that of adults, even when the children and adults have similar levels of colonization, the same prevalence of CagA and VacA, and are infected by the same H. pylori genotype (predominantly HpEurope), as we have reported for subjects living in Santiago, Chile. 13,14 Reduced gastric inflammation in H. pylori-infected children compared with infected adults also has been reported in Ghana, where residents are likely colonized by the HpAfrica strain. Role of childhood infection in the sequelae of H. pylori disease Gastric inflammation in children colonized by H. pylori is characterized by a reduction in polymorphonuclear and mononuclear cell infiltration, decreased incidence of gastroduodenal ulceration, and intact epithelium compared with that of adults.…”

“…Role of childhood infection in the sequelae of H. pylori disease Gastric inflammation in children colonized by H. pylori is characterized by a reduction in polymorphonuclear and mononuclear cell infiltration, decreased incidence of gastroduodenal ulceration, and intact epithelium compared with that of adults. 13,14 A consequence of the reduced gastric response in infected children is the absence or near absence of gastric ulceration in this age group. [16][17][18][19] Regarding duodenal ulceration, in one of the largest prospective studies to date of children with proven H. pylori infection, 19 we detected duodenal ulcer in 3.1% of the children, a prevalence considerably lower than the reported 14-15% prevalence in infected adults.…”

Immune Responses Mediated by Th17 Cells in <b><i>Helicobacter pylori </i></b>Infection

“…A positive correlation was found between age and densities of neutrophils and CD3, but not of CD8 or CD20 [22] . Children's lower level of Th17 cells and higher level of Tregs compared to those of adults may be explained by the immunosuppressive and Hp colonization advantage caused by the Treg dominance of the Th17 cell/Treg balance [2,11,23] . Homoplastically, Michalkiewicz et al [24] , observing the varieties of cytokines and the complement in gastric mucosa of Hp-infected children, found out that children's immune response to Hp infection shows specific characters: (1) Th1 expression profile, (2) lack of mRNA overexpression of natural immunity receptors, and (3) strong anti-inflammatory activities in the gastric mucosa, possibly resulting from increased activity of anti-inflammatory M2 macrophages.…”