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方面起着关键作用。 免疫反应不足可能无法控制感染，尽管在其他情况下是特定的免疫 反应可能是组织损伤和疾病的原因。大多数慢性感染患者 可能被多种生物感染；但是，多个活动之间的相互作用 感染尚不清楚，对疾病结果的影响也不明显。慢性感染，例如螺旋杆菌 幽门螺杆菌是全球发病率和死亡率相当大的原因。与急性感染不同， 可以应用“一种微生物 - 一种疾病”概念，由慢性感染生物引起的疾病 可能代表感染生物与众多宿主与环境之间的相互作用 包括与其他传染药相互作用的因素[1]。 我们和其他人在某些哥伦比亚人口中表现出了高蠕虫病的高发病率， 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 在低风险的沿海人口主要是TH2型，它可能与肠道有关 Helminthiasis。该观察结果与我们的报告是一致的，该报告表明肠系膜病减少了胃病 C57BL/6小鼠的螺旋杆菌胃炎模型中的萎缩，一种前病变[4]。我们最近的研究 在沙鼠中，显示了与幽门螺杆菌相关的与幽门螺杆菌相关的衰减，该鼠类前病变的衰减与幽门螺杆菌的衰减 Brugia 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：胃癌的发展不受影响 仅通过幽门螺杆菌的基因型（即，高胃的幽门螺杆菌菌株的能力 在低胃癌中，与幽门螺杆菌菌株相比，癌症风险区域会引起更多的亚硝化和氧化损伤 风险区域）[5]，但也通过与寄生虫感染，可以调节全身免疫 反应和TH1/TH2胃细胞因子谱。 相关性（请参阅说明）： 宿主免疫反应在确定个人如何应对慢性感染中很重要 幽门螺杆菌引起的胃。这些免疫反应在预测为什么 某些幽门螺杆菌感染的患者患胃癌。