Graduate Program in Immunology, University of Michigan , Ann Arbor, MI , USA.
Front Immunol. 2013 May 24;4:126. doi: 10.3389/fimmu.2013.00126. eCollection 2013.
Infectious pulmonary complications limit the success of hematopoietic stem cell transplantation (HSCT) as a therapy for malignant and non-malignant disorders. Susceptibility to pathogens in both autologous and allogeneic HSCT recipients persists despite successful immune reconstitution. As studying the causal effects of these immune defects in the human population can be limiting, a bone marrow transplant (BMT) mouse model can be used to understand the defect in mounting a productive innate immune response post-transplantation. When syngeneic BMT is performed, this system allows the study of BMT-induced alterations in innate immune cell function that are independent of the confounding effects of immunosuppressive therapy and graft-versus-host disease. Studies from several laboratories, including our own show that pulmonary susceptibility to bacterial infections post-BMT are largely due to alterations in the lung alveolar macrophages. Changes in these cells post-BMT include cytokine and eicosanoid dysregulations, scavenger receptor alterations, changes in micro RNA profiles, and alterations in intracellular signaling molecules that limit bacterial phagocytosis and killing. The changes that occur highlight mechanisms that promote susceptibility to infections commonly afflicting HSCT recipients and provide insight into therapeutic targets that may improve patient outcomes post-HSCT.
感染性肺部并发症限制了造血干细胞移植（HSCT）作为治疗恶性和非恶性疾病的成功。尽管免疫重建成功，但自体和同种异体 HSCT 受者对病原体仍保持易感性。由于在人类群体中研究这些免疫缺陷的因果效应可能具有局限性，因此可以使用骨髓移植（BMT）小鼠模型来了解移植后固有免疫反应产生的缺陷。当进行同基因 BMT 时，该系统允许研究 BMT 诱导的固有免疫细胞功能改变，而这些改变不受免疫抑制治疗和移植物抗宿主病的混杂影响。包括我们自己在内的几个实验室的研究表明，骨髓移植后肺部对细菌感染的易感性主要归因于肺泡巨噬细胞的改变。BMT 后这些细胞的变化包括细胞因子和类二十烷酸的失调、清道夫受体的改变、microRNA 谱的变化以及限制细菌吞噬和杀伤的细胞内信号分子的改变。发生的这些变化突出了促进感染易感性的机制，这些感染通常困扰着 HSCT 受者，并为可能改善 HSCT 后患者结局的治疗靶点提供了见解。
