ID: 218: Murine cytomegalovirus triggers interferon-β in a TLR-, RLH-, and STING-dependent manner, whereas only TLR/RLH-dependent signaling is needed for survival

Abstract

The cytomegalovirus (CMV), a member of the beta-herpesvirus family, is widely spread among the world population and causes lifelong latent infections, which can lead to severe diseases in immunocompromised patients. Therefore, it is important to understand the interplay between different immune mechanisms that are essential for the control of CMV infection. To dissect the role of different recognition platforms, MyD88Trif−/− and Cardif−/− mice devoid of TLR- or RLH-dependent signaling, respectively, or MyD88TrifCardif−/− mice and STING−/− mice were i.v. infected with mouse adapted MCMV Δ m157. 75% of MyD88TrifCardif−/− mice succumbed to CMV infection within 7 days, whereas basically all MyD88Trif−/−, Cardif−/−, and STING−/− mice survived without signs of severe disease. Nevertheless, analysis of IFN- β reporter mice with the described recognition receptor deficiencies revealed that during the early phase of infection within the liver CMV induced IFN- β in a STING-dependent manner. In contrast, in MyD88TrifCardif−/− IFN- β reporter mice an enhanced reporter induction was detected during early and late phase of infection. In lymph nodes only the second wave of IFN- β production was detectable. This lymph node-specific IFN- β induction was reduced in MyD88TrifCardif−/− mice, whereas its magnitude was comparable in STING−/− and C57BL/6 mice. In conclusion, the obtained results indicated an important, but not exclusive role of TLR- and RLH-signaling in protection against MCMV Δ m157 infection. While STING-dependent signaling was not necessary to protect against CMV infection, it seemed to be crucial for the induction of early IFN- β within the liver.