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...