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，循环质质恶性疟原虫引发了一系列事件，这些事件会触发抗原呈现细胞和自然杀手（NK）细胞（NK）细胞（NK）促炎和炎症性细胞因子的分泌。随之而来的自适应反应。尤其是NK细胞和T细胞，介导这些强大的IFN-（反应）。最后，我们将确定通过TLR通过TLR进行增强检测到介导下游IFN的差异的作用（在Fulani中的反应。越来越多的证据表明，似乎对疟疾的“抗疟疾”与强大的IFN相关的疟疾的耐药性（在Burkina faso中的众多群体都可以享受唯一的机会，这些机构是唯一的机会 - 如果这些机构可以享有这些范围 - 这些机构 - 这些机构 - 如果这些机构 - 如果这些机构 - 如果这些机构 - 如果这些机构 - 如果这些机构 - 如果这些机构 - 如果这些机构，则这些概念是如果这些机构 - 如果这些机构是众所周知的，那么如果这些机构是众多的。解释了这些有效的早期对疟疾的有效反应的基因/途径和细胞群对于支持正在进行的疫苗工作和旨在利用这些反应的新型免疫调节性的发展至关重要。