c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection

Gamma interferon (IFN-γ) plays a critical role in the early eradication of Anaplasma phagocytophilum . However, the mechanisms that regulate IFN-γ production upon infection remain poorly understood. Here we show that c-Jun NH 2 -terminal kinase 2 (JNK2) inhibits IFN-γ production during A. phagocytophilum infection. jnk2 -null mice were more refractory to infection with A. phagocytophilum and produced increased levels of IFN-γ after challenge with the pathogen. The resistance of jnk2 -null mice to A. phagocytophilum infection was due to elevated levels of IFN-γ secreted by conventional and natural killer (NK) T cells. The administration of α-galactosylceramide, a strong NK T-cell agonist, increased IFN-γ release and protected mice from A. phagocytophilum , further demonstrating the inhibitory effect of JNK2 on IFN-γ production. Collectively, these findings provide strong evidence that JNK2 is an important regulatory protein for IFN-γ secretion upon challenge with A. phagocytophilum .