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）在调节红细胞发育中起核心作用，重组EPO被广泛用于治疗促红细胞生成素不足的患者。然而，关于促红细胞生成素对非红细胞的作用，我们所知甚少。我们最近发现沙门氏菌感染诱导EPO的产生和红细胞扩增，这对细菌在体内的生长有有益的影响。总之，这些数据表明，对细菌感染的免疫反应与红细胞发育的稳态调节之间存在着令人惊讶的相互作用。我们探索性应用的目标是更详细地研究这一重要的新研究领域。鉴于红细胞免疫相互作用的新颖性和潜在重要性，我们相信对这一领域的更深入了解可能会导致细菌感染的新疫苗和治疗方法的产生。我们的申请特别提出，(i)鉴定感染期间负责EPO生产的细胞群和细菌产物，（ii）检查EPO是否对感染的免疫反应有直接和间接的影响。总的来说，我们的建议连接了两个发达但不相关的研究领域，并可能对理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意义。