Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in Mice Lacking the STING-IFNα/ß Defense Pathways.
J Immunol
; 197(6): 2338-52, 2016 09 15.
Article
in En
| MEDLINE
| ID: mdl-27511736
ABSTRACT
Type I IFN (IFN-α/ß)-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/ß signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFN-α/ß 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/ß signaling in both bone marrow-derived and -resident cells, which coalesce to support a robust HSV-1-specific CD8(+) T cell response.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon-alpha
/
Herpesvirus 1, Human
/
CD8-Positive T-Lymphocytes
/
Interferon beta-1a
/
Herpes Simplex
/
Lymphadenitis
/
Membrane Proteins
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2016
Document type:
Article