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 interferon (IFNα/β)-driven immune responses to acute viral infection are critical to counter replication and prevent dissemination. However, the mechanisms underlying host resistance to herpes simplex virus type 1 (HSV-1) are incompletely understood. Here we show that mice with deficiencies in IFNα/β signaling or STING exhibit exacerbated neurovirulence and atypical lymphotropic dissemination of HSV-1 following ocular infection. Synergy between IFNα/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 (FRC) networks in the draining lymph nodes. Our results show that resistance to HSV-1 in the TG during acute infection is conferred in part by STING and IFNα/β-signaling in both bone marrow-derived and resident cells, which coalesce to support a robust HSV-1-specific CD8+ T cell response.

Long-term consequences of topical dexamethasone treatment during acute corneal HSV-1 infection on the immune system

“…As such, we suggest the neutralization capacity, along with innate immune components also reported to be critical in viral resistance in the CNS [34], are necessary for the survival of the DEX-treated, HSV-1-infected mice.…”

The Neonatal Fc Receptor and Complement Fixation Facilitate Prophylactic Vaccine-Mediated Humoral Protection against Viral Infection in the Ocular Mucosa

“…Corneal digests were filtered through 40 μm mesh prior to labeling. Peripheral blood was collected from the facial vein and erythrocytes removed through two incubations in hypotonic lysing buffer as described (32). Cell suspensions were blocked with anti-CD16/32 (eBioscience), labeled with target-specific antibodies for twenty-thirty minutes, and washed in 1xPBS containing 1% bovine serum albumin.…”

Colony Stimulating Factor-1 Receptor Expressing Cells Infiltrating the Cornea Control Corneal Nerve Degeneration in Response to HSV-1 Infection

“… 18 , 19 Mandibular lymph node (MLN) samples were macerated, and TG samples were mechanically dissociated using a Dounce homogenizer to obtain single-cell suspensions that were filtered through a 40-μm mesh. 19 , 42 , 43 Blood samples (100 μL) were collected from the facial vein of mice using a 4-mm sterile Goldenrod animal lancet (MEDIpoint, Inc., Mineola, NY, USA), 19 mixed with 5 μL 0.5 M EDTA to prevent coagulation, and treated with 1.0 mL red cell lysing buffer (150 mM ammonium chloride, 10 mM potassium bicarbonate, and 0.1 mM EDTA), as previously descibed. 43 The single-cell suspensions from each tissue were immunostained for flow cytometric analysis.…”