IMMUNOREGULATION IN HUMAN STRONGYLOIDIASIS

描述（由申请人提供）：类圆线虫病是秘鲁一个重要的医学问题。虽然在免疫正常的宿主中，类圆线虫病症状可能是轻微的，但在免疫功能低下的个体中，它可能以严重的播散形式出现（类圆线虫过度感染）。在秘鲁，我们越来越多地观察到类圆线虫过度感染，特别是在合并感染人类嗜t淋巴细胞病毒1 （HTLV-1）的人群中。有趣的是，类圆线虫过度感染很少出现在晚期HIV/AIDS患者中。导致这些不同疾病表现的免疫学过程尚未完全了解。在我们的初步数据中，我们进行了新的观察，即圆形线虫/HTLV-1共感染的患者对圆形线虫幼虫抗原不能产生IL-5。基于这些数据，我们假设HTLV-1引起的Th1或调节反应干扰了防止过度感染的Th2反应。具体目标是：1)验证HTLV-1感染的类圆线虫病患者对特定类圆线虫抗原的免疫应答受到抑制与循环中Th1、t调节性细胞和/或调节性细胞因子的数量比正常类圆线虫病患者高相关的假设；2)验证HIV患者中类圆线虫高感染率低是由于对类圆线虫幼虫抗原保留了特异性Th2型应答的假设；3)观察HIV/HTLV-1双重感染患者的临床表现和对圆线虫幼虫抗原的免疫应答，验证HTLV-1增强HIV免疫抑制作用的假说。我们将通过前瞻性研究细胞因子对圆线虫幼虫抗原的反应来实现这些目标。我们将通过流式细胞术进一步表征负责细胞因子产生的细胞。在完成这些研究后，我们将进一步了解人类逆转录病毒感染的免疫调节作用。我们将更好地了解对圆线虫病的临床和免疫反应，并为进一步研究免疫和疫苗开发奠定基础。对类圆线虫病免疫调节的研究也可能导致解决肠道线虫负担所需的见解，肠道线虫影响数十亿人。

DESCRIPTION (provided by applicant): Strongyloidiasis is a significant medical problem in Peru. Although strongyloidiasis symptoms may be mild in immunocompetent hosts, it may present as a severe disseminated form in immunocompromised individuals (Strongyloides hyperinfection). In Peru we are increasingly observing Strongyloides hyperinfection, especially in persons co-infected with the Human T-cell-lymphotropic virus 1 (HTLV-1). Interestingly, Strongyloides hyperinfection rarely presents in persons with advanced HIV/AIDS. The immunological processes leading to these different disease manifestations are not completely understood. In our preliminary data, we made the novel observation that Strongyloides/HTLV-1 co-infected patients failed to produce IL-5 in response to Strongyloides larval antigens. Based on these data, we hypothesize that the Th1 or regulatory responses noted with HTLV-1 interfere with the Th2 responses preventing hyperinfection. The specific aims are: 1) to test the hypothesis that suppressed immune responses to specific Strongyloides larval antigens in HTLV-1 infected patients with strongyloidiasis correlate with a higher number of circulating Th1, T-regulatory cells and/or regulatory cytokines when compared to normal subjects with strongyloidiasis, 2) To test the hypothesis that the low rate of Strongyloides hyperinfection in HIV patients is due to a preserved specific Th2 type response to Strongyloides larval antigen; and 3) to characterize the clinical presentation and immune responses to Strongyloides larval antigen in patients with dual HIV/HTLV-1 infection to test the hypothesis that HTLV-1 enhances the immunosuppressive effects of HIV. We will accomplish these goals by prospectively studying cytokine responses to Strongyloides larval antigen. We will further characterize cells responsible for cytokine production by flow cytometry. In accomplishing these studies, we will advance knowledge of the immunoregulatory effects of human retroviral infections. We will better understand the clinical and immunological responses to strongyloidiasis and set the basis for further studies focusing on immunity and vaccine development. Studies of immunoregulation in strongyloidiasis may also lead to insights needed for addressing the burden of intestinal nematodes, which affect billions of people.