Pedra Joao H F, Mattner Jochen, Tao Jian, Kerfoot Steven M, Davis Roger J, Flavell Richard A, Askenase Philip W, Yin Zhinan, Fikrig Erol
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Infect Immun. 2008 Jan;76(1):308-16. doi: 10.1128/IAI.00599-07. Epub 2007 Nov 12.
Gamma interferon (IFN-gamma) plays a critical role in the early eradication of Anaplasma phagocytophilum. However, the mechanisms that regulate IFN-gamma production upon infection remain poorly understood. Here we show that c-Jun NH2-terminal kinase 2 (JNK2) inhibits IFN-gamma production during A. phagocytophilum infection. jnk2-null mice were more refractory to infection with A. phagocytophilum and produced increased levels of IFN-gamma after challenge with the pathogen. The resistance of jnk2-null mice to A. phagocytophilum infection was due to elevated levels of IFN-gamma secreted by conventional and natural killer (NK) T cells. The administration of alpha-galactosylceramide, a strong NK T-cell agonist, increased IFN-gamma release and protected mice from A. phagocytophilum, further demonstrating the inhibitory effect of JNK2 on IFN-gamma production. Collectively, these findings provide strong evidence that JNK2 is an important regulatory protein for IFN-gamma secretion upon challenge with A. phagocytophilum.
γ干扰素（IFN-γ）在嗜吞噬细胞无形体的早期清除中起关键作用。然而，感染后调节IFN-γ产生的机制仍知之甚少。在此我们表明，c-Jun氨基末端激酶2（JNK2）在嗜吞噬细胞无形体感染期间抑制IFN-γ的产生。Jnk2基因敲除小鼠对嗜吞噬细胞无形体感染更具抵抗力，在用病原体攻击后产生的IFN-γ水平升高。Jnk2基因敲除小鼠对嗜吞噬细胞无形体感染的抵抗力归因于传统和自然杀伤（NK）T细胞分泌的IFN-γ水平升高。α-半乳糖神经酰胺（一种强效的NK T细胞激动剂）的给药增加了IFN-γ的释放并保护小鼠免受嗜吞噬细胞无形体的侵害，进一步证明了JNK2对IFN-γ产生的抑制作用。总体而言，这些发现提供了强有力的证据，表明JNK2是嗜吞噬细胞无形体攻击后IFN-γ分泌的重要调节蛋白。
