Ganta Roman R, Cheng Chuanmin, Miller Elizabeth C, McGuire Bridget L, Peddireddi Lalitha, Sirigireddy Kamesh R, Chapes Stephen K
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave., Manhattan, KS 66506, USA.
Infect Immun. 2007 Jan;75(1):135-45. doi: 10.1128/IAI.01127-06. Epub 2006 Oct 23.
Human monocytic ehrlichiosis is caused by a tick-transmitted rickettsia, Ehrlichia chaffeensis. We recently reported that E. chaffeensis grown in tick cells expresses different proteins than bacteria grown in macrophages. Therefore, we tested the hypothesis that immune responses against E. chaffeensis would be different if the mice are challenged with bacteria grown in macrophages or tick cells. We assessed the E. chaffeensis clearance from the peritoneum, spleen, and liver by C57BL/6J mice using a TaqMan-based real-time reverse transcription-PCR assay. Macrophage-grown E. chaffeensis was cleared in 2 weeks from the peritoneum, whereas the pathogen from tick cells persisted for nine additional days and included three relapses of increasing bacterial load separated by three-day intervals. Tick cell-grown bacteria also persisted in the livers and spleens with higher bacterial loads compared to macrophage-grown bacteria and fluctuated over a period of 35 days. Three-day periodic cycles were detected in T-cell CD62L/CD44 ratios in the spleen and bone marrow in response to infections with both tick cell- and macrophage-grown bacteria and were accompanied by similar periodic cycles of spleen cell cytokine secretions and nitric oxide and interleukin-6 by peritoneal macrophages. The E. chaffeensis-specific immunoglobulin G response was considerably higher and steadily increased in mice infected with the tick cell-derived E. chaffeensis compared to DH82-grown bacteria. In addition, antigens detected by the immunoglobulins were significantly different between mice infected with the E. chaffeensis originating from tick cells or macrophages. The differences in the immune response to tick cell-grown bacteria compared to macrophage-grown bacteria reflected a delay in the shift of gene expression from the tick cell-specific Omp 14 gene to the macrophage-specific Omp 19 gene. These data suggest that the host response to E. chaffeensis depends on the source of the bacteria and that this experimental model requires the most natural inoculum possible to allow for a realistic understanding of host resistance.
人单核细胞埃立克体病由蜱传播的立克次氏体——查菲埃立克体引起。我们最近报道，在蜱细胞中生长的查菲埃立克体表达的蛋白质与在巨噬细胞中生长的细菌不同。因此，我们检验了这样一个假设：如果用在巨噬细胞或蜱细胞中生长的细菌攻击小鼠，那么针对查菲埃立克体的免疫反应会有所不同。我们通过基于TaqMan的实时逆转录PCR检测法，评估了C57BL/6J小鼠从腹膜、脾脏和肝脏中清除查菲埃立克体的情况。巨噬细胞中生长的查菲埃立克体在2周内从腹膜中清除，而蜱细胞中的病原体又持续存在了9天，包括细菌载量增加的三次复发，间隔为三天。与巨噬细胞中生长的细菌相比，蜱细胞中生长的细菌在肝脏和脾脏中也持续存在，细菌载量更高，且在35天内波动。在用蜱细胞和巨噬细胞中生长的细菌感染后，脾脏和骨髓中T细胞CD62L/CD44比值检测到三天的周期性循环，并伴有脾脏细胞细胞因子分泌以及腹膜巨噬细胞一氧化氮和白细胞介素-6的类似周期性循环。与感染DH82中生长的细菌相比，感染蜱细胞来源的查菲埃立克体的小鼠中，查菲埃立克体特异性免疫球蛋白G反应明显更高且稳步增加。此外，感染蜱细胞或巨噬细胞来源的查菲埃立克体的小鼠中，免疫球蛋白检测到的抗原存在显著差异。与巨噬细胞中生长的细菌相比，对蜱细胞中生长的细菌的免疫反应差异反映了基因表达从蜱细胞特异性Omp 14基因向巨噬细胞特异性Omp 19基因转变延迟。这些数据表明，宿主对查菲埃立克体的反应取决于细菌来源，并且这个实验模型需要尽可能最天然的接种物，以便对宿主抗性有现实的了解。
