Modulation of Erythropoiesis During Salmonella Infection

说明(申请人提供)：促红细胞生成素(EPO)在调节红系发育中起核心作用，重组EPO被广泛用于治疗红细胞生成不足的患者。然而，人们对EPO对非红系细胞的影响知之甚少。我们最近发现，沙门氏菌感染可诱导EPO的产生和红系的扩张，这对体内细菌的生长有有利的影响。总而言之，这些数据表明，对细菌感染的免疫反应和红系发育的动态平衡调节之间存在令人惊讶的串扰。我们在这一探索性应用中的目标是更详细地研究这一重要的新研究领域。鉴于红系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多了解可能会导致细菌感染的新疫苗和治疗方法的产生。我们的应用特别建议，(I)确定在感染过程中负责产生EPO的细胞群和细菌产物，以及(Ii)检查EPO是否对感染的免疫反应具有直接和间接影响。总体而言，我们的建议连接了两个发展良好但相互脱节的研究领域，并可能对理解红系发育如何影响对传染病的免疫反应具有更广泛的影响。

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.