Modulation of Erythropoiesis During Salmonella Infection

沙门氏菌感染期间红细胞生成的调节

• 批准号: 8400138
• 负责人: STEPHEN J MCSORLEY
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8400138
• 关键词: Affect; Anti-Inflammatory Agents; Anti-inflammatory; Area; Attention; Bacteria; Bacterial Infections; Bone Marrow; Cell Nucleus; Cell surface; Cells; Cessation of life; Clinical; Communicable Diseases; Data; Dendritic Cells; Development; Dialysis procedure; Disease; Erythrocytes; Erythroid; Erythroid Progenitor Cells; Erythropoiesis; Erythropoietin; Erythropoietin Receptor; Gastroenteritis; Generations; Goals; Growth; Human; Immune; Immune response; Immune system; Infection; Laboratories; Lead; Mus; Natural Immunity; Patients; Play; Population; Production; Receptor Signaling; Recombinant Erythropoietin; Regulation; Research; Role; Salmonella; Salmonella enterica; Salmonella infections; Salmonella typhimurium; Sanitation; Spleen; Splenomegaly; Staging; System; Systemic infection; TLR4 gene; Testing; Toll-like receptors; Typhoid Fever; Water; adaptive immunity; base; chemotherapy; cytokine; in vivo; macrophage; mouse model; novel therapeutics; novel vaccines; response

DESCRIPTION (provided by applicant): Erythropoietin (EPO) plays a central role in regulating erythroid development and recombinant EPO is widely used in patients to treat erythropoietic insufficiency. However, very little is known about the effect of EPO on non-erythroid cells. We recently found that Salmonella infection induces EPO production and erythroid expansion and that this has a beneficial effect on bacterial growth in vivo. Together, these data suggest a surprising level of crosstalk between the immune response to bacterial infection and the homeostatic regulation of erythroid development. Our goal in this exploratory application is to study this important new research area in more detail. Given the novelty and potential importance of erythroid-immune interactions, we believe greater understanding of this area could lead to the generation of new vaccines and therapeutics for bacterial infections. Our application specifically proposes to, (i) identify the cell population and bacterial products responsible for EPO production during infection, and (ii) examine whether EPO has direct and indirect effects on the immune response to infection. Overall, our proposal bridges two well-developed, but disconnected, research fields and is likely to have broader implications for understanding how erythroid development impacts immune responses to infectious disease. PUBLIC HEALTH RELEVANCE: Typhoid fever is found in geographical areas that lack clean water or basic sanitation, and affects 27.1 million people and causes 217,000 deaths annually. Splenomegaly is a prominent feature of this infection and we recently found that this is caused by expansion of erythroid progenitor cells and is advantageous for bacterial growth. Our goal in this exploratory application is to define bacterial products and cell populations that give rise to elevated EPO production and examine the effect of EPO on the innate and adaptive immune response. Given the novelty of erythroid-immune interactions, we believe greater understanding of this area could lead to the generation of new vaccines and therapeutics for bacterial infections.

描述（由申请人提供）：促红细胞生成素（EPO）在调节红细胞发育和重组EPO方面起着核心作用，可在患者中广泛用于治疗促红细胞生成不足。然而，对于EPO对非果蝇细胞的影响知之甚少。我们最近发现，沙门氏菌感染会诱导EPO产生和红细胞扩张，这对体内细菌生长具有有益作用。总之，这些数据表明对细菌感染的免疫反应与红斑发育的稳态调节之间的串扰水平令人惊讶。我们在探索性应用中的目标是更详细地研究这个重要的新研究领域。鉴于红斑 - 免疫相互作用的新颖性和潜在的重要性，我们认为对这一领域的更多了解可能会导致新的疫苗和细菌感染的治疗剂的产生。我们的应用专门提议（i）确定在感染过程中负责EPO产生的细胞群和细菌产品，以及（ii）检查EPO对感染免疫反应是否直接和间接影响。总体而言，我们的提案桥梁桥梁两个完善但已断开的研究领域，可能对了解红细胞发育如何影响对传染病的免疫反应具有更广泛的影响。 公共卫生相关性：在缺乏清洁水或基本卫生的地理区域发现伤寒，影响2710万人，每年造成217,000人死亡。脾肿大是这种感染的重要特征，我们最近发现这是由于红斑祖细胞的扩展引起的，对细菌生长有利。我们在探索性应用中的目标是定义引起的细菌产品和细胞群体 EPO产生升高并检查EPO对先天和适应性免疫反应的影响。鉴于红斑 - 免疫相互作用的新颖性，我们认为对这一领域的更多了解可能会导致新的疫苗和细菌感染的疗法。