Altered Responses to Food Proteins in Enteric Infections

描述（由申请人提供）：肠道寄生虫感染可以作为佐剂，对典型的耐受性食物抗原进行Th2偏倚反应。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引起的过敏症状和抗原特异性IgE。当蠕虫感染、过敏原致敏的小鼠被IL-10中和抗体处理后，蠕虫对过敏的依赖保护作用被取消。没有特应性的Th2反应的意外鉴定导致了蠕虫感染诱导一个特殊的树突状细胞亚群，驱动免疫调节性T细胞的产生。我们的数据为验证这一假设的理想实验模型提供了基础，在Aim 1中，我们将研究蠕虫诱导的抗过敏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提呈细胞的作用直接影响过敏原提呈。Aim 2探讨了这种可能性。在受蠕虫感染的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中提出的对感染影响口服疫苗反应的机制的特征描述，对于在发展中国家最大限度地发挥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局限于蠕虫感染，而可能是所有类型感染的共同特征，可以最大限度地提高保护性免疫，同时最大限度地减少病理。

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.