单核细胞增生性李斯特菌感染对小鼠骨髓造血干细胞的影响
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摘要
目的:探究单核细胞增生性李斯特菌感染对小鼠骨髓中造血干/祖细胞(HSPC)组成、细胞周期以及集落形成能力的影响。方法:将C57BL/6J小鼠分为感染组和对照组,感染组小鼠经腹腔注射感染单核细胞增生性李斯特菌6. 7×106CFU,对照组小鼠注射同等体积的PBS。在不同时间点检测小鼠血清中IFNγ水平,24 h后检测小鼠骨髓中HSPC组成、细胞周期以及集落形成能力,统计学处理和分析对照组与感染组之间的差异。结果:感染单核细胞增生性李斯特菌24 h后,血清IFNγ水平达到高峰;与对照组相比,小鼠骨髓细胞中LSK、处于S期的LSK以及短期造血干细胞(ST-HSC)的比例显著升高(P <0. 001),长期造血干细胞(LT-HSC)以及处于S期的LT-HSC的比例明显升高(P <0. 01),骨髓细胞集落形成能力明显降低(P <0. 01)。结论:感染单核细胞增生性李斯特菌后,小鼠骨髓造血干细胞由静止进入增殖状态,细胞集落形成能力下降。这提示,单核细胞增生性李斯特菌感染可引起造血干细胞耗竭。
Objective: To investigate the effects of Listeria monocytogenes infection on hematopoietic stem and progenitor cell(HSPC) composition, cell cycle and cell colony-forming ability in mouse bone marrow. Methods: The C57 BL/6 J mice were divided into infected group and control group. The mice in injected group were infected intraperitoneally with 6.7 × 10~6 CFU Listeria monocytogenes, while the mice in control group were injecfed with PBS of same volume. The serum levels of IFNγ were detected at different time points. After 24 hours, the HS/PC composition,cell cycle and cell colony-forming ability in bone marrow of mice were measured, and the difference between the control group and the infected group was statistically analyzed. Results: Serum IFNγ levels peaked at 24 hours after infection with Listeria monocytogenes. After 24 h, the proportion of LSK, LSK in S phase, and short-term hematopoietic stem cells(STHSC) in the infected group were significantly higher than those in the control group(P <0.001),long-term hematopoietic stem cells(LT-HSC) and the proportion of LT-HSC in S phase were significantly increased(P <0.01),and the cell colony-forming ability of bone marrow significantly decreased(P< 0. 01). Conclusion : After infection with Listeria monocytogenes, bone marrow hematopoietic stem cells enter the proliferative state from rest, the cell colony-forming ability decreases,suggesting that Listeria monocytogenes infection can cause hematopoietic stem cell depletion.
Objective: To investigate the effects of Listeria monocytogenes infection on hematopoietic stem and progenitor cell(HSPC) composition, cell cycle and cell colony-forming ability in mouse bone marrow. Methods: The C57 BL/6 J mice were divided into infected group and control group. The mice in injected group were infected intraperitoneally with 6.7 × 10~6 CFU Listeria monocytogenes, while the mice in control group were injecfed with PBS of same volume. The serum levels of IFNγ were detected at different time points. After 24 hours, the HS/PC composition,cell cycle and cell colony-forming ability in bone marrow of mice were measured, and the difference between the control group and the infected group was statistically analyzed. Results: Serum IFNγ levels peaked at 24 hours after infection with Listeria monocytogenes. After 24 h, the proportion of LSK, LSK in S phase, and short-term hematopoietic stem cells(STHSC) in the infected group were significantly higher than those in the control group(P <0.001),long-term hematopoietic stem cells(LT-HSC) and the proportion of LT-HSC in S phase were significantly increased(P <0.01),and the cell colony-forming ability of bone marrow significantly decreased(P< 0. 01). Conclusion : After infection with Listeria monocytogenes, bone marrow hematopoietic stem cells enter the proliferative state from rest, the cell colony-forming ability decreases,suggesting that Listeria monocytogenes infection can cause hematopoietic stem cell depletion.
引文
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2 de Noordhout CM,Devleesschauwer B,Angulo FJ,et al.The global burden of listeriosis:a systematic review and meta-analysis.Lancet Infect Dis,2014;14(11):1073-1082.
3 Cellin BG,Broome CV.Listeriosis.JAMA,1989;261(9):1313-1320.
4 Conlan JW.Early host-pathogen interactions in the liver and spleen during systemic murine listeriosis:an overview.Immunobiology,1999;201(2):178-187.
5 Cossart P.Illuminating the landscape of host-pathogen interactions with the bacterium Listeria monocytogenes.Proc Natl Acad Sci USA,2011;108(49):19484-19491.
6 Cheshier SH,Morrison SJ,Liao X,et al.In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells.Proc Natl Acad Sci USA,1999;96(6):3120-3125.
7 Baldridge MT,King KY,Boles NC,et al.Quiescent haematopoietic stem cells are activated by IFN-γin response to chronic infection.Nature,2010;465(7299):793-797.
8 Matatall KA,Shen CC,Challen GA,et al.Type II interferon promotes differentiation of myeloid-biased hematopoietic stem cells.Stem Cells,2014;32(11):3023-3030.
9 Zhao X,Ren G,Liang L,et al.Brief report:interferon-γinduces expansion of Lin-Sca-1+C-kit+cells.Stem Cells,2010;28(1):122-126.