Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses

Abstract

Together our data suggest that H. pylori induces a regulatory T cell response, possibly contributing to its peaceful coexistence with the human host, and that ulcers occur when this regulatory response is inadequate.

Coadaptation of Helicobacter pylori and humans: ancient history, modern implications

“…The direct importance of the acquired immune response in pathogenesis is evidenced by the observation that the Th1 cytokine IFN-γ induces gastric atrophy in mice, even in the absence of Helicobacter species, although infection potentiates this effect (S40). In humans, Th responses are less polarized than in mice, and patients with peptic ulcers have both stronger Th1 and Th2 gastric responses to H. pylori antigens than do colonized patients without ulcers (70). At a population level, the IgG subclass response to H. pylori suggests a Th2 bias in parts of Africa and a Th1 bias in Japan and the United Kingdom, possibly contributing to the lower disease prevalence in Africa (71) (S38, S41).…”

“…Finally, changes in immunity may be important. Patients with peptic ulceration have an impaired gastric mucosal Treg response, compared with H. pylori-positive persons without ulcers (70). Gradual reduction in colonization with other microbes over the late 19th and early 20th century or improvement in nutrition may have led to a less mature Treg response in some hosts, predisposing to increased gastric inflammation and peptic ulceration ( Figure 5).…”

“…Collectively, these data suggest that H. pylori-responsive gastric Tregs are important both in promoting persistence and in controlling inflammation (and disease) (S36) ( Figure 5). Importantly, patients with peptic ulcer disease have many fewer gastric mucosal Tregs than H. pylori-positive patients without peptic ulcers (70).…”

Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance

“…It is typically acquired in early childhood (1) and, in the absence of antibiotic therapy, may persist for the entire lifespan of the host (2, 3). The extraordinary ability of H. pylori to resist a vigorous adaptive immune response driven in large part by T-helper 1 (Th1) and/or T-helper 17 (Th17)-polarized effector T cells (4,5) has been attributed to its perfect adaptation to-and manipulation of-the human innate and adaptive immune systems (6). H. pylori has colonized its human host for at least 60,000 y (7) and during this long period of coevolution has evolved elaborate ways to systemically manipulate adaptive immune responses and to promote its persistence through the preferential induction of regulatory T-cell (Treg) over T-effector cell responses.…”

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

“…In the vast majority of cases, however, colonization leads to asymptomatic chronic gastritis, with increased infiltration of neutrophils, dendritic cells (DCs), macrophages, natural killer (NK) cells, and lymphocytes into the gastric mucosa (reviewed in Robinson and Atherton, 2010;Koch et al, 2013). There is increased abundance of pro-inflammatory T-helper 1 (Th1) and Th17 subsets, as well as anti-inflammatory regulatory T cells (Tregs) (Lundgren et al, 2005;Robinson et al, 2008;Serrano et al, 2013). Infected individuals without gastroduodenal disease tend to have a more robust Treg response, which may also provide protection against extra-gastric conditions such as asthma, allergy, and inflammatory bowel disease (Kao et al, 2010;Arnold et al, 2011Arnold et al, , 2012Wang et al, 2013;Amberbir et al, 2014).…”