Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection

Sci Adv. 2024 Nov 22;10(47):eadn6379. doi: 10.1126/sciadv.adn6379. Epub 2024 Nov 20.

Abstract

Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T cell infiltration of the retina and marked gliosis. Blocking immune responses generally, or via targeting the chemokine receptor CXCR3, did not exacerbate retinal disease but instead prevented pathology despite retinal MCMV infection. Thus, our data establish this model for studies of congenital retinal disease and show that the immune system drives pathology in the neonatal eye after MCMV infection.

MeSH terms

  • Animals
  • Animals, Newborn*
  • Chorioretinitis* / immunology
  • Chorioretinitis* / pathology
  • Chorioretinitis* / virology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Retinitis / immunology
  • Cytomegalovirus Retinitis / pathology
  • Cytomegalovirus Retinitis / virology
  • Disease Models, Animal
  • Humans
  • Mice
  • Muromegalovirus* / immunology
  • Muromegalovirus* / physiology
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Retina* / immunology
  • Retina* / pathology
  • Retina* / virology
  • T-Lymphocytes / immunology

Substances

  • Receptors, CXCR3
  • Cxcr3 protein, mouse