Innate Immune Responses in Populations with Differing Susceptibility to Malaria

不同疟疾易感性人群的先天免疫反应

• 批准号: 8479313
• 负责人: SUNIL PARIKH
• 金额: $ 15.97万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-05 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8479313
• 关键词: Accounting; Africa; Anti-Inflammatory Agents; Anti-inflammatory; Antigen-Presenting Cells; Antigens; Antimalarials; Blood; Burkina Faso; Cells; Cessation of life; Characteristics; Child; Clinical; Collaborations; Communicable Diseases; Detection; Development; Disease; Disease Outcome; Effectiveness; Effector Cell; Employee Strikes; Equilibrium; Erythrocytes; Ethnic group; Event; Gene Expression Profile; Genes; Genome; Human; Humoral Immunities; Immune response; Immunity; Incidence; Infection; Inflammatory; Inflammatory Response; Interferons; Knockout Mice; Lead; Life; Link; Malaria; Mediating; Modeling; Molecular Profiling; Morbidity - disease rate; Mus; Natural Immunity; Natural Killer Cells; Parasitemia; Parasites; Pathology; Pathway interactions; Peripheral Blood Mononuclear Cell; Plasmodium falciparum; Population; Predisposition; Prevalence; Receptor Activation; Recurrence; Relative (related person); Reporting; Resistance; Resolution; Role; Severities; Source; Staging; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; TLR2 gene; TLR4 gene; Toll-like receptors; Transcript; Vaccines; arm; base; clinically significant; cytokine; experience; improved; killer T cell; mortality; novel; pathogen; response; therapeutic vaccine; vaccine development

DESCRIPTION (provided by applicant: During the initial stages of infection, circulating Plasmodium falciparum parasites initiate a cascade of events that trigger antigen presenting cells and natural killer (NK) cells to secrete both pro-inflammatory and anti-inflammatory cytokines. The characteristics of these innate immune responses appear to be a critical step in determining control of parasitemia, severity of infection, and the effectiveness of ensuing adaptive responses. In Burkina Faso, the two main ethnic groups, the Fulani and Mossi, have a differential ability to control parasitemia which appears to be mediated by differences in early IFN-( associated responses. Through a whole genome transcriptional approach, we aim to understand critical gene expression patterns which account for the effective early IFN-( responses in the Fulani. We will extend these studies by defining the role of critical cellular subsets, notably NK cells and T cells, in mediating these robust IFN-( responses. Lastly, we will determine the role of enhanced detection of blood stage parasite through TLRs in mediating the differential downstream IFN-( responses in the Fulani. With growing evidence of what appears to be a "hard-wired" resistance to malaria associated with robust IFN-( responses, the ethnic groups in Burkina Faso offers a unique opportunity to delineate the mechanisms underlying these protective early IFN-( responses. Understanding the key genes/pathways and cell populations that account for these effective early responses to malaria is vital to supporting ongoing vaccine efforts and the development of novel immunomodulatory aimed at harnessing these responses.

描述（由申请人提供）：在感染的初始阶段，循环的恶性疟原虫寄生虫启动一系列事件，触发抗原呈递细胞和自然杀伤（NK）细胞分泌促炎和抗炎细胞因子。这些先天免疫反应的特征似乎是决定寄生虫病控制、感染严重程度和随后适应性反应有效性的关键步骤。在布基纳法索，富拉尼族（Fulani）和莫西族（Mossi）这两个主要族群控制寄生虫病的能力不同，这似乎是由早期IFN相关反应的差异所介导的。通过全基因组转录方法，我们旨在了解富拉尼人有效的早期IFN-(反应的关键基因表达模式。我们将通过定义关键细胞亚群，特别是NK细胞和T细胞，在介导这些强大的IFN-（）反应中的作用来扩展这些研究。最后，我们将确定通过tlr增强对血期寄生虫的检测在富拉尼人体内介导不同下游IFN-(反应中的作用。随着越来越多的证据表明，对疟疾的“天生”抵抗力似乎与强大的干扰素反应有关，布基纳法索的种族群体提供了一个独特的机会来描述这些保护性的早期干扰素反应的机制。了解这些有效的疟疾早期反应的关键基因/途径和细胞群对于支持正在进行的疫苗工作和开发旨在利用这些反应的新型免疫调节剂至关重要。