PATHOGENESIS OF HUMAN GRANULOCYTIC EHRLICHIOSIS

描述（改编自申请人摘要）：人粒细胞 埃立克体病（HGE）是一种急性发热性疾病，2年前在 明尼苏达州和威斯康星州，现在迅速出现在地区， 可能是传染媒介硬蜱 HGE出现在血液粒细胞中， 白细胞和血小板计数下降，可导致严重的 并发症 诊断一直很困难，血清学检测，使用 来自感染相关马埃里希体的马的白细胞， 在介绍时不敏感。 申请人最近分离出病原体 通过在HL 60细胞中培养从患者中分离HGE试剂（Goodman，et al， 1996年）。 此外，申请人还种植了E.马（Munderloh等， 1996年），现在HGE，在I.肩胛肌细胞系，在那里它发展出不同的 比在人类细胞中。 这些发现为研究提供了基础 旨在更好地了解代理的生物学。 在他的实验室里， HGE现在也在其假定的天然靶细胞--人骨中生长 骨髓祖细胞，伴有粒细胞和单核细胞感染 和前体。 申请人的研究还强烈表明，唾液酸 刘易斯x（CD 15 s），存在于两种细胞类型，是一种主要的细胞 HGE的表面受体。 该药剂表现出独特的铁/铁载体 相互作用，并且似乎能够在内体中存活。 I. 用培养的HGE感染肩胛骨，并用于蜱叮咬感染 仓鼠（导致与人类相似的血液结果）。 的 然后从受感染的仓鼠中重新分离出病原体，完成其生命周期。 基于HGE的IFA和免疫印迹分析已经发展到开始定义 主要的免疫原，它们在感染期间的时间演变，以及可能的 蜱与人细胞中抗原表达的差异。 Working in an 地方病流行区，申请人已经组成了一个多学科的团队， 在这些进步中迅速。 古德曼博士的目标是：1）描述， 在分子水平上，HGE试剂与其人 靶细胞和受体，2）表征生物学关键 HGE与蜱载体及培养蜱细胞相互作用及比较 这些相互作用与人类细胞中定义的相互作用，以及3）识别和 描述HGE的关键抗原蛋白和对HGE的免疫应答。 这些抗原。

DESCRIPTION (Adapted from the applicant's abstract): Human granulocytic ehrlichiosis (HGE) is an acute febrile illness described 2 years ago in Minnesota and Wisconsin and now rapidly emerging in areas infested by its likely vector, Ixodes ticks. HGE appears in blood granulocytes, causes depression of leukocyte and platelet counts, and can result in serious complications. Diagnosis has been difficult and serologic testing, using leukocytes from horses infected with the related Ehrlichia equi, is insensitive at presentation. The applicant recently isolated the etiologic agent of HGE from patients by cultivation in HL60 cells (Goodman, et al, 1996). In addition, the applicant has grown E. equi (Munderloh et al, 1996), and now HGE, in I. scapularis cell lines, where it develops different forms than in human cells. These findings provided the basis for studies aimed at better understanding the biology of the agent. In his laboratory, HGE has now also been grown in its presumed natural target cells, human bone marrow progenitors, with infection of both granulocytic and monocytic cells and precursors. The applicant's studies also strongly suggest that sialyl Lewis x (CD15s), which is present on both cell types, is a major cell surface receptor for HGE. The agent manifests unique iron/siderophore interactions and appears capable of survival within endosomes. I. scapularis was infected with cultured HGE and used to tick bite infect hamsters (resulting in blood findings similar to those in humans). The agent was then reisolated from infected hamsters, completing its life-cycle. HGE-based IFA and immunoblot assays have been developed to begin to define major immunogens, their temporal evolution during infection, and possible differences in antigenic expression in tick vs. human cells. Working in an endemic area, the applicant has formed a multidisciplinary team to build rapidly upon these advances. Dr. Goodman's aims are: 1) to characterize, at the molecular level, the interaction of the HGE agent with both its human target cells and receptor(s), 2) to characterize the biologically critical interaction of HGE with its tick vector and cultured tick cells and compare these interactions with those defined in human cells and 3) to identify and characterize the key antigenic proteins of HGE and the immune response to these antigens.