发光激活转染杀伤细胞监测全身细菌和真菌感染期间白细胞的迁移。
Luminescent-activated transfected killer cells to monitor leukocyte trafficking during systemic bacterial and fungal infection.
机构信息
Department of Medicine, Division of General Internal Medicine, Los Angeles Biomedical Research Institute, Harbor-University of California at Los Angeles Medical Center, Torrance, CA, USA.
出版信息
J Infect Dis. 2012 Jan 15;205(2):337-47. doi: 10.1093/infdis/jir725. Epub 2011 Nov 28.
BACKGROUND
Activated transfected killer (ATAK) cells are immortal phagocytes transfected with a luminescence reporter that effectively treat lethal infections in neutropenic mice. Their in vivo trafficking, lifespan, and immunogenicity are unknown.
METHODS
Mice were made neutropenic; infected or not with Staphylococcus aureus, Acinetobacter baumannii, Candida albicans, or Aspergillus fumigatus; and treated intraperitoneally with ATAK cells. Cell trafficking and lifespan were assessed by in vivo imaging and reverse transcription-polymerase chain reaction.
RESULTS
In uninfected neutropenic mice, ATAK cells spread from the mesentery into visceral organs on days 1-3. Splenic accumulation of ATAK cells increased at day 1 after infection with S. aureus and A. baumannii, and kidney accumulation increased in mice infected with C. albicans. Lung accumulation was seen at day 3 in mice infected by inhalation with A. fumigatus. By day 8, coincident with increasing anti-ATAK antibodies, luminescence signal was lost and there was no detectable mRNA transcription from ATAK cells.
CONCLUSIONS
ATAK cells accumulated in target organs with distinct profiles, depending on the microbial etiology of infection. Finally, generation of an anti-ATAK immune response may provide an important safety mechanism that helps clear the cells from the host as the marrow recovers.
背景
转染激活的杀伤（ATAK）细胞是一种永生化吞噬细胞，转染了发光报告基因，能有效治疗中性粒细胞减少症小鼠的致死性感染。但其体内迁移、寿命和免疫原性尚不清楚。
方法
使小鼠中性粒细胞减少；用金黄色葡萄球菌、鲍曼不动杆菌、白色念珠菌或烟曲霉感染或不感染；并用 ATAK 细胞腹腔内治疗。通过体内成像和逆转录聚合酶链反应评估细胞迁移和寿命。
结果
在未感染的中性粒细胞减少症小鼠中，ATAK 细胞在第 1-3 天从肠系膜扩散到内脏器官。在感染金黄色葡萄球菌和鲍曼不动杆菌后第 1 天，脾中 ATAK 细胞的积累增加，而在感染白色念珠菌的小鼠中，肾脏的积累增加。在感染烟曲霉的小鼠中，在第 3 天可见肺部积累。到第 8 天，随着抗 ATAK 抗体的增加，发光信号消失，从 ATAK 细胞中无法检测到可转录的 mRNA。
结论
ATAK 细胞根据感染的微生物病因在靶器官中积累，具有不同的特征。最后，抗 ATAK 免疫反应的产生可能是一种重要的安全机制，有助于在骨髓恢复时清除宿主中的细胞。
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