Altered Responses to Food Proteins in Enteric Infections

肠道感染中食物蛋白质反应的改变

基本信息

批准号：
7663954
负责人：
CATHRYN R NAGLER
金额：
$ 28.7万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7663954
关键词：
Adjuvant Aftercare Agreement Allergens Allergic Antibody Formation Antigen-Presenting Cells Antigens Attention B-Lymphocytes C3H/HeJ Mouse Cells Cholera Toxin Chronic Clinical DNA Data Dendritic Cells Development Enteral Epidemiologic Studies Experimental Models Food Food Hypersensitivity Funding Generations Growth Helminths Hypersensitivity IgE Immune Immune response Immunity Immunoglobulin G Immunosuppression Individual Infection Inflammatory Interleukin-10 Laboratories Mediating Mediator of activation protein Modeling Mus Oral Parasites Pathology Peanuts - dietary Proteins Reporting Role Salmonella Signal Transduction Source Suggestion Symptoms T-Lymphocyte TLR2 gene TLR4 gene Testing Vaccines Work atopy base immunogenic immunoregulation insight mutant neutralizing antibody novel oral vaccine prevent research study response vaccine efficacy

项目摘要

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（由申请人提供）：肠道寄生虫感染可以作为佐剂，引发对典型耐受性形式的饮食抗原的 Th2 偏向反应。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以预防食物过敏模型中诱发的过敏症状和抗原特异性 IgE。当用 IL-10 中和抗体治疗感染蠕虫、过敏原致敏的小鼠时，依赖蠕虫的抗过敏保护被消除。出人意料地鉴定出没有特应性的 Th2 反应，这表明蠕虫感染会诱导一种特殊的树突状细胞亚群，从而驱动免疫调节 T 细胞的产生。我们的数据为检验这一假设的理想实验模型提供了基础。目标1，我们将检查蠕虫诱导的过敏保护是否可归因于分泌IL-10的T细胞。蠕虫感染还可能通过其对抗原呈递细胞的影响直接影响过敏原的呈递。目标 2 探讨了这种可能性。在蠕虫感染个体中观察到的口服疫苗反应受损也可能是蠕虫诱导的免疫抑制的结果。正如目标 3 中所提出的，表征感染影响口服疫苗反应的机制对于最大限度地提高发展中国家的疫苗效力具有实际意义。慢性肠道感染诱导免疫调节介质不太可能仅限于蠕虫感染，而可能是所有类型感染的共同特征，可最大限度地提高保护性免疫力，同时最大限度地减少病理。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Functional aspects of the mucosal immune system.

粘膜免疫系统的功能方面。

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Nagler
通讯作者：
Nagler

Vaccine-induced antibody isotypes are skewed by impaired CD4 T cell and invariant NKT cell effector responses in MyD88-deficient mice.

MyD88 缺陷小鼠中受损的 CD4 T 细胞和不变的 NKT 细胞效应反应会扭曲疫苗诱导的抗体同种型。

DOI：
发表时间：
2009-08-15
期刊：
影响因子：
0
作者：
Iweala, Onyinye I;Smith, Donald W;Matharu, Kabir S;Sada;Nguyen, Deanna D;Dekruyff, Rosemarie H;Umetsu, Dale T;Behar, Samuel M;Nagler, Cathryn R
通讯作者：
Nagler, Cathryn R

Immune privilege in the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora.

肠道免疫特权：对饮食抗原和共生菌群无反应的建立和维持。