STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus.
Pia-Katharina TegtmeyerJulia SpanierKatharina BorstJennifer BeckerAndré RiedlChristoph HircheLuca GhitaJennifer SkerraKira BaumannSiegfried WeissMarius DöringZsolt RuzsicsUlrich KalinkePublished in: Nature communications (2019)
Cytomegalovirus is a DNA-encoded β-herpesvirus that induces STING-dependent type 1 interferon responses in macrophages and uses myeloid cells as a vehicle for dissemination. Here we report that STING knockout mice are as resistant to murine cytomegalovirus (MCMV) infection as wild-type controls, whereas mice with a combined Toll-like receptor/RIG-I-like receptor/STING signaling deficiency do not mount type 1 interferon responses and succumb to the infection. Although STING alone is dispensable for survival, early IFN-β induction in Kupffer cells is STING-dependent and controls early hepatic virus propagation. Infection experiments with an inducible reporter MCMV show that STING constrains MCMV replication in myeloid cells and limits viral dissemination via these cells. By contrast, restriction of viral dissemination from hepatocytes to other organs is independent of STING. Thus, during MCMV infection STING is involved in early IFN-β induction in Kupffer cells and the restriction of viral dissemination via myeloid cells, whereas it is dispensable for survival.
Keyphrases
- induced apoptosis
- dendritic cells
- cell cycle arrest
- toll like receptor
- immune response
- sars cov
- endoplasmic reticulum stress
- acute myeloid leukemia
- oxidative stress
- stem cells
- signaling pathway
- type diabetes
- wild type
- magnetic resonance imaging
- cell therapy
- skeletal muscle
- nuclear factor
- diffuse large b cell lymphoma
- smoking cessation
- high fat diet induced