NK cells use perforin rather than granulysin for anticryptococcal activity
NK cells use perforin rather than granulysin for anticryptococcal activity
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DOI：
10.4049/jimmunol.173.5.3357
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Mody, CH
中科院分区：
文献类型：
--
作者：
Ma, LL;Wang, CLC;Mody, CH
细胞毒性淋巴细胞具有直接杀死微生物的能力;然而，所涉及的机制知之甚少。使用新型隐球菌，这可能会导致致命的真菌感染的HIV感染患者，我们以前的研究表明，颗粒溶素是必要的，而穿孔素是不必要的，CD 8 T淋巴细胞真菌杀伤。相比之下，NK细胞发挥其抗微生物活性的机制尚不清楚，特别是，颗粒溶解素和穿孔素对NK介导的抗真菌活性的贡献是未知的。原代人NK细胞和人NK细胞系YT被发现组成型表达颗粒溶素和穿孔素，并具有抗隐球菌活性，相反，CD 8 T淋巴细胞，这需要刺激。当颗粒溶素蛋白和mRNA被颗粒溶素小干扰RNA阻断时，NK细胞介导的抗真菌作用不受影响，与在CD 8 T淋巴细胞中观察到的废除活性相反。然而，当穿孔素被抑制的concanamycin A，并沉默使用发夹小干扰RNA，NK细胞的抗隐球菌活性被废除。此外，当颗粒溶素和穿孔素都被抑制时，NK细胞的抗隐球菌活性并不比单独沉默穿孔素进一步降低。这些结果表明，在NK细胞中的抗真菌活性是组成型表达的，而CD 8 T淋巴细胞中，它需要事先激活，穿孔素，而不是颗粒溶素，发挥主导作用的NK细胞抗隐球菌活性，而CD 8 T淋巴细胞中，颗粒溶素，而不是穿孔素，发挥主导作用的抗隐球菌活性。
Cytotoxic lymphocytes have the capacity to kill microbes directly; however, the mechanisms involved are poorly understood. Using Cryptococcus neoformans, which causes a potentially fatal fungal infection in HIV-infected patients, our previous studies showed that granulysin is necessary, while perforin is dispensable, for CD8 T lymphocyte fungal killing. By contrast, the mechanisms by which NK cells exert their antimicrobial activity are not clear, and in particular, the contribution of granulysin and perforin to NK-mediated antifungal activity is unknown. Primary human NK cells and a human NK cell line YT were found to constitutively express granulysin and perforin, and possessed anticryptococcal activity, in contrast to CD8 T lymphocytes, which required stimulation. When granulysin protein and mRNA were blocked by granulysin small interfering RNA, the NK cell-mediated antifungal effect was not affected in contrast to the abrogated activity observed in CD8 T lymphocytes. However, when perforin was inhibited by concanamycin A, and silenced using hairpin small interfering RNA, the anticryptococcal activities of NK cells were abrogated. Furthermore, when granulysin and perforin were both inhibited, the anticryptococcal activities of the NK cells were not reduced further than by silencing perforin alone. These results indicate that the antifungal activity is constitutively expressed in NK cells in contrast to CD8 T lymphocytes, in which it requires prior activation, and perforin, but not granulysin, plays the dominant role in NK cell anticryptococcal activity, in contrast to CD8 T lymphocytes, in which granulysin, but not perforin, plays the dominant role in anticryptococcal activity.