| First Author | Royer DJ | Year | 2016 |
| Journal | J Immunol | Volume | 197 |
| Issue | 6 | Pages | 2338-52 |
| PubMed ID | 27511736 | Mgi Jnum | J:345260 |
| Mgi Id | MGI:6835378 | Doi | 10.4049/jimmunol.1600574 |
| Citation | Royer DJ, et al. (2016) Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNalpha/beta Defense Pathways. J Immunol 197(6):2338-52 |
| abstractText | Type I IFN (IFN-alpha/beta)-driven immune responses to acute viral infection are critical to counter replication and prevent dissemination. However, the mechanisms underlying host resistance to HSV type 1 (HSV-1) are incompletely understood. In this study, we show that mice with deficiencies in IFN-alpha/beta signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFN-alpha/beta signaling and efficacy of early adaptive immune responses to HSV-1 were dissected using bone marrow chimeras and adoptive cell transfer approaches to profile clonal expansion, effector function, and recruitment of HSV-specific CD8(+) T cells. Lymphotropic viral dissemination was commensurate with abrogated CD8(+) T cell responses and pathological alterations of fibroblastic reticular cell networks in the draining lymph nodes. Our results show that resistance to HSV-1 in the trigeminal ganglia during acute infection is conferred in part by STING and IFN-alpha/beta signaling in both bone marrow-derived and -resident cells, which coalesce to support a robust HSV-1-specific CD8(+) T cell response. |
