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- Title
Mesenchymal stem cells detect and defend against gammaherpesvirus infection via the cGAS-STING pathway.
- Authors
Li, Meiyu; Wu, Minhao; Wang, Yi; Huang, Xi; Yang, Kun; Wang, Jinli
- Abstract
Mesenchymal stem cells (MSCs) are widely used in clinical settings to treat tissue injuries and autoimmune disorders due to their multipotentiality and immunomodulation. Long-term observations reveal several complications after MSCs infusion, especially herpesviral infection. However, the mechanism of host defense against herpesviruses in MSCs remains largely unknown. Here we showed that murine gammaherpesvirus-68 (MHV-68), which is genetically and biologically related to human gammaherpesviruses, efficiently infected MSCs both in vitro and in vivo. Cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) was identified as the sensor of MHV-68 in MSCs for the first time. Moreover, the cytosolic DNA sensing pathway mediated a potent anti-herpesviral effect through the adaptor STING and downstream kinase TBK1. Furthermore, blockade of IFN signaling suggested that cytosolic DNA sensing triggered both IFN-dependent and -independent anti-herpesviral responses. Our findings demonstrate that cGAS-STING mediates innate immunity to gammaherpesvirus infection in MSCs, which may provide a clue to develop therapeutic strategy.
- Subjects
MURINE gammaherpesvirus diseases; AUTOIMMUNE disease treatment; MESENCHYMAL stem cells; CYTOMEGALOVIRUSES; HEMATOPOIETIC stem cell transplantation; THERAPEUTICS
- Publication
Scientific Reports, 2015, p7820
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep07820