IMMUNOREGULATION IN HUMAN STRONGYLOIDIASIS

人类圆线虫病的免疫调节

• 批准号: 7278190
• 负责人: Martin Montes
• 金额: $ 5.12万
• 依托单位: UNIVERSIDAD PERUANA CAYETANO HEREDIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278190
• 关键词: AIDS/HIV problem; Address; Adrenal Cortex Hormones; Affect; Africa; Antigens; Area; Bacterial Infections; CD4 Positive T Lymphocytes; Cancer Patient; Caribbean natives; Caribbean region; Cells; Chronic; Clinical; Cohort Studies; Communicable Diseases; Complement; Data; Disease; Flow Cytometry; Frequencies; Goals; HIV; HIV Infections; Helminths; Hemorrhage; Human; Human T-lymphotropic virus 1; Immune response; Immunity; Immunocompetent; Immunocompromised Host; Immunosuppression; Individual; Infection; Infection Control; Institutes; Interleukin-2; Interleukin-5; Intestines; Japan; Knowledge; Larva; Lead; Life Cycle Stages; Lung; Lymphocyte; Medical; Mucosal Immunity; Mus; Nematoda; Numbers; Opportunistic Infections; Parasites; Patients; Persons; Peru; Population; Process; Production; Range; Rate; Research Personnel; Retroviridae; Severities; South America; Staging; Strongyloides; Strongyloides stercoralis; Strongyloidiasis; Structure; Symptoms; T-Cell Proliferation; T-Lymphocyte; Testing; Transcriptional Activation; Up-Regulation; Viral Load result; base; cell killing; cytokine; eosinophil; gastrointestinal; granulocyte; immunoregulation; insight; novel; prevent; prospective; receptor; response; transmission process; vaccine development

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.

描述（由申请人提供）：类圆线虫病是秘鲁的一个重大医疗问题。尽管类圆线虫病的症状在免疫功能正常的宿主中可能较轻微，但在免疫功能低下的个体中可能表现为严重的播散性形式（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，特别是在同时感染人类 T 细胞淋巴细胞病毒 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艾滋病毒/艾滋病患者中。导致这些不同疾病表现的免疫过程尚未完全了解。在我们的初步数据中，我们进行了新的观察，即类圆线虫/HTLV-1 共感染患者未能产生针对类圆线虫幼虫抗原的 IL-5。基于这些数据，我们假设 HTLV-1 引起的 Th1 或调节反应会干扰 Th2 反应，从而防止过度感染。具体目的是：1) 检验以下假设：与正常的类圆线虫病受试者​​相比，HTLV-1 感染的类圆线虫病患者对特定类圆线虫幼虫抗原的抑制免疫反应与较高数量的循环 Th1、T 调节细胞和/或调节性细胞因子相关，2) 检验 HIV 患者中类圆线虫过度感染率较低的假设 是由于对类圆线虫幼虫抗原保留了特异性 Th2 型反应； 3) 表征 HIV/HTLV-1 双重感染患者的临床表现和对类圆线虫幼虫抗原的免疫反应，以检验 HTLV-1 增强 HIV 免疫抑制作用的假设。我们将通过前瞻性研究细胞因子对类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。在完成这些研究的过程中，我们将增进对人类逆转录病毒感染的免疫调节作用的了解。我们将更好地了解类圆线虫病的临床和免疫反应，并为重点关注免疫和疫苗开发的进一步研究奠定基础。对类圆线虫病免疫调节的研究也可能为解决影响数十亿人的肠道线虫负担提供所需的见解。