Altered Responses to Food Proteins in Enteric Infections

肠道感染中食物蛋白质反应的改变

• 批准号: 6973978
• 负责人: CATHRYN R NAGLER
• 金额: $ 28.64万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6973978
• 关键词: antigen presentation; autoimmunity; dendritic cells; drug screening /evaluation; enzyme linked immunosorbent assay; flow cytometry; food hypersensitivity; gastrointestinal infection; genetically modified animals; helminthiasis; host organism interaction; immunocytochemistry; immunoregulation; interleukin 10; laboratory mouse; neutralizing antibody; oral administration; parasitic gastrointestinal disorder; pathologic process; polymerase chain reaction; protozoal vaccine; terminal nick end labeling; tissue /cell culture

DESCRIPTION (provided by applicant): Infection with an enteric parasite can act as an adjuvant to prime for a Th2 biased response to a typically tolerogenic form of dietary antigen. However, in agreement with recent clinical and epidemiological studies, we have found that helminth infection protects against the anaphylactic symptoms and antigen specific IgE induced in a model of food allergy. Helminth dependent protection against allergy was abrogated when helminth infected, allergen sensitized mice were treated with neutralizing antibodies to IL-10. The unexpected identification of Th2 responses without atopy has led to the suggestion that helminth infection induces a specialized subset of dendritic cells that drive the generation of immunoregulatory T cells. Our data provide the basis for an ideal experimental model in which to test this hypothesis, hi Aim 1 we will examine whether helminth-induced protection against allergy is attributable to IL-10 secreting T cells. Helminth infection may also influence allergen presentation directly, via its effects on antigen presenting cells. This possibility is explored in Aim 2. The impaired responsiveness to oral vaccines observed in helminth-infected individuals may also be a consequence of helminth-induced immunosuppression. Characterization of the mechanisms by which infection influences the response to oral vaccines, as proposed in Aim 3 has practical implications for maximizing vaccine efficacy in the developing world. The induction of immunoregulatory mediators by chronic enteric infection is not likely to be restricted to helminth infection but may be a feature common to all types of infection that serves to maximize protective immunity while minimizing pathology.

描述（由申请方提供）：肠道寄生虫感染可作为佐剂，引发对典型致耐受性形式的饮食抗原的Th 2偏向性应答。然而，与最近的临床和流行病学研究一致，我们发现蠕虫感染可预防食物过敏模型中诱导的过敏性症状和抗原特异性IgE。当蠕虫感染时，蠕虫依赖性的抗过敏保护被废除，过敏原致敏的小鼠用IL-10的中和抗体处理。Th 2反应的意外鉴定无特应性导致了蠕虫感染诱导树突状细胞的特化亚群驱动免疫调节性T细胞的产生的建议。我们的数据提供了一个理想的实验模型的基础，在该模型中测试这一假设。在目的1中，我们将检查蠕虫诱导的针对变态反应的保护是否归因于分泌IL-10的T细胞。蠕虫感染也可能通过其对抗原呈递细胞的作用直接影响变应原呈递。目标2探讨了这种可能性。在蠕虫感染个体中观察到的对口服疫苗的反应性受损也可能是蠕虫诱导的免疫抑制的结果。目标3中提出的感染影响口服疫苗反应的机制的特征对于在发展中国家最大限度地提高疫苗效力具有实际意义。慢性肠道感染诱导的免疫调节介质不太可能仅限于蠕虫感染，但可能是所有类型感染的共同特征，其用于最大化保护性免疫，同时最小化病理。