Immune Response to H. Pylori Infection

对幽门螺杆菌感染的免疫反应

• 批准号: 8320334
• 负责人: JAMES G FOX
• 金额: $ 28.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320334
• 关键词: Acute; Adult; Aftercare; Anthelmintics; Area; Atrophic Gastritis; Brugia; Brugia pahangi; C57BL/6 Mouse; Child; Chronic; Coculture Techniques; Colombia; Disease; Disease Outcome; Environmental Risk Factor; Epithelial Cells; Gene Expression; Genetic Transcription; Genotype; Gerbils; Helicobacter Infections; Helicobacter Pylori-Associated Gastritis; Helicobacter pylori; Helminthiasis; Helminths; Human; Immune response; Incidence; Individual; Infection; Infection Control; Infectious Agent; Instruction; Integration Host Factors; Intestines; Lesion; Life; Locales; Microbe; Morbidity - disease rate; Mus; Nematospiroides dubius; Organism; Parasites; Pathogenesis; Patients; Play; Population; Premalignant; Reporting; Risk; Role; Stomach; Stomach Carcinoma; Testing; Tissues; attenuation; cancer risk; cytokine; high risk; in vivo; malignant stomach neoplasm; mortality; mouse model; oxidative damage

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.

宿主免疫反应在确定慢性感染的疾病表现中起着至关重要的作用。 免疫反应不足可能无法控制感染，尽管在其他情况下，特异性免疫 反应可能是组织损伤和疾病的原因。大多数患者患有慢性感染 可能被不止一种生物体感染；然而，多个主动之间的相互作用 感染情况尚不清楚，对疾病结果的影响也不清楚。慢性感染，例如螺杆菌 幽门螺杆菌是世界范围内相当大的发病率和死亡率的原因。与急性感染不同， 可应用“一种微生物-一种疾病”概念，慢性传染性微生物引起的疾病更多 可能代表感染生物体与众多宿主和环境之间的相互作用 因素包括与其他传染源的相互作用[1]。 我们和其他人已经证明了哥伦比亚特定人群中蠕虫病的高发病率， 特别是儿童 (2,3]。我们的初步研究 [2] 表明对幽门螺杆菌感染的免疫反应 在低风险沿海人群中，Th2 型占主导地位，可能与肠道相关 蠕虫病。这一观察结果与我们的报告一致，即肠道蠕虫病减少了胃 萎缩是螺杆菌胃炎 C57BL/6 小鼠模型中的一种癌前病变 [4]。我们最近的研究 在沙鼠中显示出与幽门螺杆菌相关的恶变前病变的减弱 布鲁贾属sp。也支持这一假设。 在这些拟议的研究中，我们将检验以下假设：胃癌的进展不受影响 仅取决于幽门螺杆菌的基因型（即，来自高胃粘膜区域患者的幽门螺杆菌菌株的能力） 在低位胃癌中，与幽门螺杆菌菌株相比，癌症风险区域会造成更多的亚硝化和氧化损伤 危险区域）[5]，但也通过同时感染可以调节全身免疫的寄生虫 反应和 Th1/Th2 胃细胞因子谱。 相关性（参见说明）： 宿主免疫反应对于确定个体如何应对慢性感染非常重要。 胃病是由幽门螺杆菌引起的。这些免疫反应在预测原因方面发挥着关键作用 某些幽门螺杆菌感染患者会发展为胃癌。