Viruses (Aug 2024)

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

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

DOI
https://doi.org/10.3390/v16091363
Journal volume & issue
Vol. 16, no. 9
p. 1363

Abstract

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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.

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