title: Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/β Defense Pathways.
abstract: Type I IFN (IFN-α/β)-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-α/β signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFN-α/β 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-α/β signaling in both bone marrow-derived and -resident cells, which coalesce to support a robust HSV-1-specific CD8(+) T cell response.
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors: Derek J
authors: 0000-0002-8476-1784
authors: DJ
authors: Royer
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and.
authors: Christopher D
authors: CD
authors: Conrady
authors: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104 Dan-Carr@ouhsc.edu.
authors: Daniel J J
authors: DJ
authors: Carr
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005123:Eye / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D000068556:Interferon beta-1a / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008199:Lymphadenitis / Q000276:immunology* / Q000503:physiopathology / Q000821:virology*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction; D012668:Trigeminal Ganglion / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D014779:Virus Replication; D000099197:STING Protein
chemical_list: D000068556:Interferon beta-1a; D016898:Interferon-alpha; D008565:Membrane Proteins; C530855:Sting1 protein, mouse; D000099197:STING Protein