Modulation of Erythropoiesis During Salmonella Infection

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重要作用，重组EPO广泛用于治疗红细胞生成不足的患者。然而，关于EPO对非红系细胞的作用知之甚少。我们最近发现沙门氏菌感染诱导EPO产生和红系细胞扩增，这对体内细菌生长具有有益作用。总之，这些数据表明细菌感染的免疫应答和红细胞发育的稳态调节之间存在令人惊讶的串扰水平。我们在这个探索性的应用程序的目标是更详细地研究这个重要的新的研究领域。鉴于红细胞免疫相互作用的新奇和潜在重要性，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）鉴定在感染期间负责EPO产生的细胞群和细菌产物，和（ii）检查EPO是否对感染的免疫应答具有直接和间接作用。总的来说，我们的提议连接了两个发展良好但互不相关的研究领域，并且可能对理解红细胞发育如何影响对传染病的免疫反应产生更广泛的影响。

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.