Invasion and intracellular development of the human granulocytic ehrlichiosis agent in tick cell culture
Invasion and intracellular development of the human granulocytic ehrlichiosis agent in tick cell culture
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DOI：
10.1128/jcm.37.8.2518-2524.1999
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发表时间：
1999-08-01
影响因子：
9.4
通讯作者：
Goodman, JL
中科院分区：
文献类型：
--
作者：
Munderloh, UG;Jauron, SD;Goodman, JL
人嗜粒细胞埃立克体是由蜱传播的细菌病原体，可引起急性、危及生命的疾病，即人粒细胞埃立克体病（HGE）。侵入蜱叮咬部位的嗜中性粒细胞内的埃立克体可能被媒介摄入，在蜱的下一次血液餐中传播给另一个哺乳动物宿主。因此，载体中的复制和发育循环是哺乳动物感染的先决条件，但这些事件尚未被描述。我们报告了直接从受感染的马和狗中分离的两种HGE试剂株的蜱细胞培养物，并且还在蜱细胞中建立了来自HL 60培养物的人分离物，证明了HGE试剂的血液阶段对蜱细胞具有感染性，正如在人细胞系HL 60中复制的那些。这需要改变培养系统，包括新的蜱细胞系。在蜱细胞层中，HGE试剂诱导感染灶，导致坏死斑块和最终破坏培养物。使用人分离株和电子显微镜，我们监测粘附，内化和复制的载体蜱细胞。这两种电子透明和致密的形式坚持和进入细胞的机制让人想起吞噬作用。埃里希体细胞分裂后不久开始，导致内体充满了许多埃里希体。在早期发育过程中，具有紧密细胞壁的苍白埃里希体占主导地位，但到第2天，单个细菌浓缩成具有波纹膜的深色形式。这些可能会被压缩成团块，其中单个生物体几乎无法辨别。这些是否是埃立克体生命周期的一部分或正在退化尚不清楚。
Human granulocytotropic ehrlichias are tick-borne bacterial pathogens that cause an acute, life-threatening illness, human granulocytic ehrlichiosis (HGE). Ehrlichias within neutrophil granulocytes that invade tick bite sites are likely ingested by the vector, to be transmitted to another mammalian host during the tick's next blood meal. Thus, the cycle of replication and development in the vector is prerequisite to mammalian infection, and yet these events have not been described. We report tick cell culture isolation of two strains of the HGE agent directly from an infected horse and a dog and have also established a human isolate from HL60 culture in tick cells, proving that the blood stages of the HGE agent are infectious for tick cells, as are those replicating in the human cell line HL60. This required changes to the culture system, including a new tick cell line. In tick cell layers, the HGE agent induced foci of infection that caused necrotic plaques and eventual destruction of the culture. Using the human isolate and electron microscopy, we monitored adhesion, internalization, and replication in vector tick cells. Both electron-lucent and -dense forms adhered to and entered cells by a mechanism reminiscent of phagocytosis. Ehrlichial cell division was initiated soon after, resulting in endosomes filled with numerous ehrlichias. During early development, pale ehrlichias with a tight cell wall dominated, but by day 2, individual bacteria condensed into dark forms with a rippled membrane. These may become compacted into clumps where individual organisms are barely discernible. Whether these are part of an ehrlichia life cycle or are degenerating is unknown.