INFLAMMATORY MONOCYTES IN ALLO-HSCT

循环单核细胞分化为组织巨噬细胞和树突状细胞， 防御微生物病原体。血液中的单核细胞由具有不同免疫反应的亚群组成。 分化潜力和贩运模式。循环单核细胞亚群的重建 异基因造血干细胞移植（allo-HSCT）后的患者之间，我们假设 这对感染的易感性有影响。我们研究的目的是描述 不同单核细胞亚群在小鼠抗烟曲霉感染中的作用 真菌感染模型和异基因造血干细胞移植（allo， HSCT）。我们的第一个目标是表征小鼠中的循环和组织炎症单核细胞， HSCT。将研究MCP-1对CCR 2介导的组织单核细胞再增殖的贡献 将确定移植后GVHD对该过程的影响。康贝特人将以 肺移植小鼠对烟曲霉菌肺部感染易感性及相关因素研究 易感性与炎性单核细胞的存在和激活状态有关。我们的第二个目标是 表征炎性单核细胞介导抗侵袭性真菌感染的能力， allo-HSCT设置。我们将在体外从骨髓前体细胞产生鼠单核细胞亚群， 研究它们介导抗烟曲霉感染保护的能力。重组 将向移植小鼠施用趋化因子和生长因子， 单核细胞重建天然免疫受体介导的信号转导对单核细胞介导的 将研究同种异体移植环境中的抗真菌防御。我们的第三个目标是前瞻性地 研究allo-HSCT受者单核细胞亚群频率和功能，并将其与 真菌感染的发展。此外，我们将研究骨髓和外周血干细胞 同种异体移植物中是否存在单核细胞亚群。从移植物和allo-HSCT中分离单核细胞 患者和他们的能力。将调查烟曲霉分生孢子和菌丝。相关性：The 这些研究的结果可能为未来的临床方案提供基础，以研究 分化的单核细胞为异基因干细胞移植患者，以增强对真菌的抵抗力 病原体

Circulating monocytes differentiate into tissue macrophages and dendritic cells that provide immune defense against microbial pathogens. Monocytes in the bloodstream consist of subpopulations with distinct differentiation potentials and trafficking patterns. Reconstitution of circulating monocyte subsets varies between patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and we postulate that this has implications for susceptibility to infection. The goal of our studies is to characterize the contribution of distinct monocyte subsets to defense against Aspergillus fumigatus infection in a murine model of fungal infection and ip humans following allogeneic hematopoietic stem cell transplantation (allo- HSCT). Our first aim is to characterize circulating and tissue inflammatory monocytes in mice following allo- HSCT. The contribution of MCP-1to CCR2-mediated monocyte repopulation of tissues will be investigated following transplantation and the impact of GVHD on this process will be determined. We will determine the susceptibility of transplanted mice to pulmonary infection with Aspergillus fumigatus and correlate susceptibility with the presence and activation status of inflammatory monocytes. Our second aim is to characterize the ability of inflammatory monocytes to mediate protection against invasive fungal infection in the allo-HSCT setting. We will generate murine monocyte subsets in vitro from bone marrow precursors and investigate their ability to mediate protection against Aspergillus fumigatus infections. Recombinant chemokines and growth factors will be administered to transplanted mice to accelerate and enhance monocyte reconstitution. The impact of innate immune receptor mediated signaling on monocyte mediated antifungal defense in the allo-transplant setting will be investigated. Our third aim is to prospectively investigate monocyte subset frequencies and function in allo-HSCT recipients and correlate these with development of fungal infections. In addition, we will investigate bone marrow and peripheral blood stem cell allografts for the presence of monocyte subsets. Monocyteswill be isolated from grafts and from allo-HSCT patients and their ability to inactivate A. fumigatus conidia and hyphae will be investigated. Relevance: The results of these studies may provide a foundation for future clinical protocols to investigate the infusion of differentiated monocytes into allogeneic stem cell transplant patients to enhance resistance to fungal pathogens..