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.

宿主免疫反应在决定慢性感染的疾病表现中起着至关重要的作用。 免疫反应不充分可能无法控制感染，尽管在其他情况下，特定的免疫 反应可能是导致组织损伤和疾病的原因。大多数慢性感染患者 很可能被一种以上的生物感染；然而，多个活跃的 感染尚不清楚，对疾病结局的影响也不清楚。幽门螺杆菌等慢性感染 幽门螺杆菌是全世界相当大的发病率和死亡率的原因。与急性感染不同的是， “一菌一病”的概念可以适用，慢性传染病引起的疾病更多 可能代表了感染的有机体(S)与多种宿主和环境之间的相互作用 因素包括与其他传染病病原体的相互作用[1]。 我们和其他人已经证明了蠕虫病在哥伦比亚特定人群中的高发病率， 尤其是儿童(2，3)。我们的初步研究[2]表明，幽门螺杆菌感染的免疫反应 在低危沿海人群中，主要是Th2型，可能与肠道有关 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部 萎缩，一种癌前病变，在C57BL/6小鼠幽门螺杆菌胃炎模型中[4]。我们最近的研究 在显示幽门螺杆菌感染的沙土鼠癌前病变减轻的沙土鼠中， 布鲁氏菌(Brugia sp.)也支持这一假设。 在这些拟议的研究中，我们将检验进展为胃癌不受影响的假设。 仅根据幽门螺杆菌的基因型别(即来自高胃区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，癌症风险区域会导致更多的亚硝酸盐和氧化损伤 风险区域)[5]，但也与寄生虫合并感染有关，这种寄生虫可以调节系统免疫 反应和Th1/Th2胃细胞因子谱。 相关性(请参阅说明)： 宿主免疫反应在决定个体如何应对慢性感染方面很重要。 幽门螺杆菌引起的胃。这些免疫反应在预测原因中起着关键作用 某些感染幽门螺杆菌的患者会患上胃癌。