| First Author | Hsia HC | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 101 |
| Issue | 4 | Pages | 1053-1064 |
| PubMed ID | 27965384 | Mgi Jnum | J:243048 |
| Mgi Id | MGI:5907540 | Doi | 10.1189/jlb.4A1016-199RR |
| Citation | Hsia HC, et al. (2017) Signal transducer and activator of transcription 3 (Stat3) regulates host defense and protects mice against herpes simplex virus-1 (HSV-1) infection. J Leukoc Biol 101(4):1053-1064 |
| abstractText | Signal transducer and activator of transcription 3 (STAT3) mediates cellular responses to multiple cytokines, governs gene expression, and regulates the development and activation of immune cells. STAT3 also modulates reactivation of latent herpes simplex virus-1 (HSV-1) in ganglia. However, it is unclear how STAT3 regulates the innate immune response during the early phase of HSV-1 lytic infection. Many cell types critical for the innate immunity are derived from the myeloid lineage. Therefore, in this study, we used myeloid-specific Stat3 knockout mice to investigate the role of STAT3 in the innate immune response against HSV-1. Our results demonstrate that Stat3 knockout bone marrow-derived macrophages (BMMs) expressed decreased levels of interferon-alpha (IFN-alpha) and interferon-stimulated genes (ISGs) upon HSV-1 infection. In vivo, knockout mice were more susceptible to HSV-1, as marked by higher viral loads and more significant weight loss. Splenic expression of IFN-alpha and ISGs was reduced in the absence of STAT3, indicating that STAT3 is required for optimal type I interferon response to HSV-1. Expression of TNF-alpha and IL-12, cytokines that have been shown to limit HSV-1 replication and pathogenesis, was also significantly lower in knockout mice. Interestingly, Stat3 knockout mice failed to expand the CD8+ conventional DC (cDC) population upon HSV-1 infection, and this was accompanied by impaired NK and CD8 T cell activation. Collectively, our data demonstrate that myeloid-specific Stat3 deletion causes defects in multiple aspects of the immune system and that STAT3 has a protective role at the early stage of systemic HSV-1 infection. |
