Immune Response to H. Pylori Infection

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The host immune response plays a critical role in determining disease manifestations of chronic infections. Inadequate immune response may fail to control infection, although in other cases the specific immune response may be the cause of tissue damage and disease. The majority of patients with chronic infections are likely to be infected by more than one organism; however, the interaction between multiple active infections is not known, nor is the impact on disease outcome clear. Chronic infections such as Helicobacter pylori are the cause of considerable morbidity and mortality, worldwide. Unlike acute infections, where the "one microbe- one disease" concept can be applied, disease caused by chronic infectious organisms more likely represents interactions between the infecting organism(s) and a multitude of hosts and environmental factors including interaction with other infectious agents [1]. We and others have demonstrated the high incidence of helminthiasis in select Colombian populations, particularly children (2,3]. Our preliminary studies [2] suggest that the immune response to H. pylori infection in the low-risk coastal population is predominantly type Th2 and that it may be related to intestinal helminthiasis. This observation is consistent with our report that intestinal helminthiasis reduced gastric atrophy, a premalignant lesion, in the C57BL/6 mouse model of Helicobacter gastritis [4]. Our recent studies in gerbils demonstrating an H. pylori-associated attenuation of premalignant lesions in gerbils coinfected with Brugia sp. also support this hypothesis. In these proposed studies, we will test the hypothesis that progression to gastric cancer is influenced not only by the genotype of H. pylori (i.e., the ability of H. pylori strains from patients in regions of high gastric cancer risk areas to cause more nitrosative and oxidative damage vs. H. pylori strains in low gastric cancer risk areas) [5], but also by concun-ent infection with parasites which can modulate systemic immune responses and the Th1/Th2 gastric cytokine profile. RELEVANCE (See Instructions): The host immune response is important in determining how an individual responds to the chronic infection in the stomach caused by Helicobacter pylori. These immune responses play a critical role in predicting why certain patients with H. pylori infection develop gastric cancer.