Journal Article

Fas/FasL-Mediated Apoptosis and Inflammation Contribute to Recovery from HSV-2-Mediated Spinal Cord Infection

Krzyzowska, Malgorzata, Skulska, Katarzyna, Patrycy, Magdalena, Kowalczyk, Andrzej, Eriksson, Kristina, Janicka, Martyna, Chodkowski, Marcin, Thörn, Karolina

2024

Overview

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that causes a persistent infection in sensory ganglia. The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection.

• Publisher: MDPI AG,MDPI
• Subject: Animal models / Animals / Antibodies / Antiviral agents / Antiviral drugs / Apoptosis / Astrocytes / CD4 antigen / CD4-positive T-lymphocytes / Cell death / Central nervous system diseases / Chemokines / chronic diseases / Cloning / Complications and side effects / Cytokines - metabolism / death domain receptors / Development and progression / Disease Models, Animal / Disease transmission / Fas Ligand Protein - genetics / Fas Ligand Protein - metabolism / fas Receptor - genetics / fas Receptor - metabolism / Fas/FasL / FasL protein / Female / Glial cells / Health aspects / Herpes / Herpes simplex / Herpes Simplex - immunology / Herpes Simplex - virology / Herpes viruses / Herpesvirus 2, Human - immunology / Herpesvirus 2, Human - physiology / Herpesvirus diseases / HSV-2 / Human alphaherpesvirus 2 / Immune response / Immunologi inom det medicinska området / Immunology in the Medical Area / Infections / Inflammation / Inflammation - virology / Invoices / Lymphocytes T / Meningitis / Mice / Mice, Knockout / Microglia / Microglia - immunology / Microglia - metabolism / Microglia - virology / Monocytes / Morbidity / mortality / pathogens / Penicillin / Sensory neurons / Software / Spinal cord / Spinal Cord - immunology / Spinal Cord - pathology / Spinal Cord - virology / Tumor necrosis factor / Tumor necrosis factor-TNF / viral load