The role of NK cell-derived interferon-γ in HSV-induced encephalitis Katharina Borst1, Chintan Chhatbar1, Andreas Pavlou1, Luca Ghita1, Ulrich Kalinke1 1TWINCORE - Centre for Experimental and Clinical Infection Research, Institute for Experimental Infection Research, Hannover, Germany
NK cells are part of the innate immune system and constitute the first line of defense upon viral infections. They elicit cytotoxic functions and produce IFN-γ. Although IFN-γ is mostly known to play an important role during bacterial infection, it is also a key player during anti-viral immune responses. Patients suffering from NK cell deficiency also experience increased recurring, and more severe susceptibility to diverse herpes virus infections, including herpes simplex virus (HSV) infection. Specifically, herpes simplex encephalitis (HSE) is a severe disease and the most common sporadic viral encephalitis in the Western world. Untreated HSE is lethal in 70 to 80% of the cases. Most treated individuals survive the infection, however, sequelae among survivors are significant and more than 50% of the patients show severe deficits. The importance of NK cell-derived IFN-γ during HSE is largely unknown. To analyze the importance of NK cell-derived IFN-γ in HSV-induced encephalitis, we created IFN-γOFF mice, in which the IFN-γ gene function can be reconstituted in a Cre-dependent manner. Such mice were intercrossed with Ncr1-Cre-/+ mice to generate mice in which only NK cells can produce IFN-γ (IFN-γNcr1-ON). Ex vivo stimulation of IFN-γNcr1-ON-derived splenocytes and subsequent intracellular IFN-γ staining by FACS verified the specificity of NK cell-derived IFN-γ reconstitution. Of note, during homeostasis no detrimental effect on the immune cell compartment was detected in IFN-γOFF andIFN-γNcr1-ON mice. Such mice will now be used to dissect the role of NK cell derived IFN-γ during HSE.
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