Quantitative Evaluation of Inflammatory and Immune Responses in the Early Stages of ChronicHelicobacter pyloriInfection

Abstract

The early consequences of Helicobacter pylori infection and the role of bacterial virulence determinants in disease outcome remain to be established. The present study sought to measure the development of host inflammatory and immune responses and their relationship to the putative bacterial virulence factors cag pathogenicity island (cagPAI), vacA allele, and oipA in combination with bacterial colonization density in a feline model of the early stages of H. pylori infection. Gastric tissues obtained from infected and uninfected cats were evaluated for H. pylori ureB, cagPAI, vacA allele, and oipA and colonization density (urease, histology, and real-time PCR). Inflammation was assessed by measuring mRNA upregulation of gamma interferon (IFN-␥), interleukin (IL)-1␣, IL-1␤, IL-4, IL-6, IL-8, IL-10, and IL-12 p40 and histopathology. The mucosal immune response was characterized by morphometric analysis of lymphoid follicles and by differentiating lymphocyte populations with antibodies against surface markers. Infecting H. pylori strains were positive for vacAs1 but lacked cagPAI and an active oipA gene. Colonization density was uniform throughout the stomach. Upregulation of IFN-␥, IL-1␣, IL-1␤, and IL-8 and increased severity of inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area of lymphoid aggregates were 5 and 10 times greater, respectively, in the stomachs of infected than uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and B220 but negative for CD3 and CD79␣, whereas in infected cats they were frequent and positive for BLA.36, CD79␣, and CD3 but negative for B220. Upregulation of IFN-␥, IL-1␣, IL-1␤, and IL-8 and marked hyperplasia of secondary lymphoid follicles are early consequences of H. pylori infection in cats. The response appears to be similar to that of infected people, particularly children, can develop independently of the pathogenicity factors cagPAI and oipA, and is not correlated with the degree of colonization density or urease activity.Helicobacter pylori is a gram-negative bacterium that chronically infects more than half of all people worldwide (6,66,69,75). Infection tends to begin in infancy (new infections are uncommon in adults) and is likely to last for decades (16).Over a span of 20 to 30 years, about one in six H. pyloriinfected adults in the West develops duodenal ulcers that are associated with antral predominant gastritis and increased acid secretion (18). Another smaller subset of people develop atrophy and intestinal metaplasia of the body of the stomach and go on to develop gastric carcinoma over a period of 30 to 40 years (55). While the factors determining this variable outcome are not well understood, the development of a sustained gastric inflammatory and immune response to infection appears to be pivotal for the development of disease (12,49,55,56). Chronic infection of adults with H. pylori is characterized by the infiltration of polymorphonuclear and mononuclear cells an...

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

“…Otherwise, H. pylori DNA was not detected in the liver of patients with alcoholic cirrhosis and those with autoimmune hepatitis. In agreement with previous studies (Straubinger et al 2003, Algood & Cover 2006, Lafdil et al 2010, we confirmed the strong Th1 proinflammatory response with increased levels of IFN-γ, the Th1 signature cytokine, in these patients. We F: female; M: male; n: number of subjects; SD: standard deviation.…”

“…IL-10 can suppress the immune response against pathogens, including those of the genus Helicobacter (Algood & Cover 2006), mainly by inhibiting IFN-γ. IFN-γ is considered an essential molecule for the control of intracellular pathogens, but also acts against Helicobacter (D'Elios et al 1997, Straubinger et al 2003. The recently discovered pro-inflammatory Th17 cell and its major inflammatory cytokine, IL-17A, have the capacity to confer protection against extracellular bacteria, among them, H. pylori (Caruso et al 2007).…”

Mucosal defence along the gastrointestinal tract of cats and dogs

“…The gastric lymphoid follicles consist mainly of IgM + B cells surrounded by clusters of CD4 + and CD8 + T cells [21]. More recent studies [47] have sought to characterise the cellular and cytokine changes in gastric tissues that occur during the early stage of infection in cats. The initial mucosal response was associated with an increase in the levels of IFNγ, IL1α, IL-1β and IL-8 mRNA with secondary lymphoid follicles infiltrated with BLA.36 positive cells (progenitor B cells), CD79α positive cells (reactive B cells), and CD3 positive T cells.…”

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

“…In particular, the pluripotent pro-inflammatory cytokine IL-1b has a central role in the pathogenesis of Helicobacter pylori-induced mucosal inflammation (Guiraldes et al, 2001;Maeda et al, 2001;Straubinger et al, 2003). IL-1b gene expression and protein production are increased in H. pylori infection and reduced with successful eradication (Wang et al, 1999).…”