Expansion of 2B4+ natural killer (NK) cells and decrease in NKp46+ NK cells in response to influenza
Expansion of 2B4+ natural killer (NK) cells and decrease in NKp46+ NK cells in response to influenza
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DOI：
10.1111/j.1365-2567.2010.03394.x
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发表时间：
2011-04-01
期刊：
影响因子：
6.4
通讯作者：
Altfeld, Marcus
中科院分区：
文献类型：
--
作者：
Jost, Stephanie;Reardon, Jeff;Altfeld, Marcus
一些研究强调了小鼠自然杀伤细胞（NK）在控制流感病毒感染中的重要性，特别是通过天然细胞毒性受体NKp46。然而，对NK细胞在人类流感感染中的作用知之甚少。本研究表明，在体外暴露于流感后，NK细胞上NKp46的表达降低，而2B4的表达上调，2B4是一种激活受体，可以与NKp46协同增强自然细胞毒性。与这些观察结果一致，NKp46（暗）和2B4（亮）NK细胞分别比表达高水平NKp46或低水平2B4的NK细胞对流感的反应具有更高的功能活性。重要的是，我们评估了这些受体的表达是否在体内对流感抗原的反应中也被修饰，并显示肌肉注射流感疫苗后，表达2b4的NK细胞增加，表达NKp46(+) NK细胞减少。总之，我们的研究结果进一步表明，NKp46可能在人类流感的先天免疫应答中发挥重要作用，并揭示暴露于流感抗原与先前未被识别的2B4表达增加有关，从而影响NK细胞对病毒的活性。
P>Several studies have highlighted the importance of murine natural killer (NK) cells in the control of influenza virus infection, notably through the natural cytotoxicity receptor NKp46. However, little is known about the involvement of NK cells in human influenza infection. Here, we show that upon in vitro exposure to influenza, NKp46 expression on NK cells decreases, whereas expression of 2B4, an activating receptor that can enhance natural cytotoxicity in synergy with NKp46, is up-regulated. Consistent with these observations, NKp46(dull) and 2B4(bright) NK cells had a higher functional activity in response to influenza than NK cells expressing high levels of NKp46 or low levels of 2B4, respectively. Importantly, we assessed whether the expression of these receptors was also modified in vivo in response to influenza antigens and showed that an increase in 2B4-expressing NK cells and a decrease in NKp46(+) NK cells occurred following intramuscular influenza vaccination. Altogether, our results further suggest that NKp46 may play an important role in the innate immune response to human influenza and reveal that exposure to influenza antigens is associated with a previously unrecognized increase in 2B4 expression that can impact NK cell activity against the virus.