Mihret Adane, Mamo Gezahagne, Tafesse Mesfin, Hailu Asrat, Parida Shreemanta
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
BMC Res Notes. 2011 Jul 21;4:247. doi: 10.1186/1756-0500-4-247.
Dendritic cells (DCs) can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood.
To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p < 0.05) up regulation following infection with M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS) from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation.
These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.
树突状细胞(DCs)能够摄取一系列不同的抗原,包括微生物,并且它们处理和呈递这些抗原的效率比任何其他抗原呈递细胞都更高。然而,人类DC与结核分枝杆菌之间的相互作用究竟是被入侵宿主的一种防御机制,还是帮助入侵者逃避宿主的防御机制,目前仍不清楚。
为了分析结核分枝杆菌与免疫细胞之间的相互作用,用结核分枝杆菌H37Rv野生型菌株感染人外周血单核细胞来源的未成熟DCs,并使用流式细胞术分析细胞表面表达标志物。还利用5,6-羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)稀释技术研究了被结核分枝杆菌感染的DC诱导T细胞增殖的能力。发现DCs能够内化分枝杆菌,并在不同感染复数下呈现剂量依赖性感染和坏死。对感染DC中细胞表面表达标志物CD40、CD54、CD80、CD83、CD86和HLA DR进行流式细胞术分析,结果显示与未受刺激的未成熟DC相比,结核分枝杆菌感染后这些标志物有显著上调(p < 0.05)。来自马流产沙门氏菌的脂多糖(LPS)是一种已知的DC成熟剂,用作阳性对照,其细胞表面标志物上调情况与结核分枝杆菌感染的DC相当。结果表明,被结核分枝杆菌感染的DC能诱导T细胞增殖。
这些数据清楚地表明,结核分枝杆菌在体外可诱导人单核细胞来源的未成熟DC活化和成熟,并诱导T细胞增殖。