Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

Abstract

Disease due to the gastric pathogen Helicobacter pylori varies in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model of H. pylori gastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-␥) is essential for induction of gastritis but showed that IFN-␥-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-␥. Tumor necrosis factor alpha (TNF-␣) and IL-17F were also elevated in association with disease. These results indicate that while H. pylori-specific CD4 ؉ T cells and IFN-␥ are both essential for induction of gastritis due to H. pylori, IFN-␥ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-␣, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due to H. pylori is associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.

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).…”

“…It is known that the infection by the bacterium is accompanied by a Th1 immune response that, instead of being useful for clearing the bacterium, is probably responsible for the mucosa damage (1). The paradigm that the Th1 profile is the only one that sustains H. pylori-associated diseases has been recently revised, because it has been demonstrated that other proinflammatory cytokines, besides IFN-g, such as IL-17 and TNF-a, are also involved (2).…”

Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis

“…Th1 and Th17 cells are also associated with the gastric mucosal immune response elicited by H. pylori infection (Gray et al, 2013). It is therefore interesting that infected mice had reduced numbers of these cells in the spleen and CNS after EAE induction.…”

The synergy of Helicobacter pylori and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer

“…[9,10] The phenotypes of T helper subsets are determined by the local cytokine milieu and their lineage-specific transcription factors. [11][12][13] H. pylori elicits Th1 response to produce interferon-γ and tumor necrosis factor-α causing chronic gastritis and ulcers. [9,13] Th17 cells are also frequently recruited by H. pylori to the gastric mucosa, and are characterized by expression of interleukin (IL)-17A/F, granulocytemacrophage colony-stimulating factor (GM-CSF), IL-21, IL-22 and IL-23, and the transcription factor of RORγt.…”

“…[11][12][13] H. pylori elicits Th1 response to produce interferon-γ and tumor necrosis factor-α causing chronic gastritis and ulcers. [9,13] Th17 cells are also frequently recruited by H. pylori to the gastric mucosa, and are characterized by expression of interleukin (IL)-17A/F, granulocytemacrophage colony-stimulating factor (GM-CSF), IL-21, IL-22 and IL-23, and the transcription factor of RORγt. [11,14] While activation of Th17 cells contributes to bacterial eradication, [15] Th17-mediated immuneresponse can be detrimental to gastric epithelium during gastritis.…”