Functional Fc receptors are crucial in antibody-mediated protection against cytomegalovirus

Eur J Immunol. 2024 Oct;54(10):e2451044. doi: 10.1002/eji.202451044. Epub 2024 Jul 16.

Abstract

Human cytomegalovirus is a medically important pathogen. Previously, using murine CMV (MCMV), we provided evidence that both neutralizing and nonneutralizing antibodies can confer protection from viral infection in vivo. In this study, we report that serum derived from infected animals had a greater protective capacity in MCMV-infected RAG-/- mice than serum from animals immunized with purified virus. The protective activity of immune serum was strictly dependent on functional Fcγ receptors (FcγR). Deletion of individual FcγRs or combined deletion of FcγRI and FcγRIV had little impact on the protection afforded by serum. Adoptive transfer of CD115-positive cells from noninfected donors demonstrated that monocytes represent important cellular mediators of the protective activity provided by immune serum. Our studies suggest that Fc-FcγR interactions and monocytic cells are critical for antibody-mediated protection against MCMV infection in vivo. These findings may provide new avenues for the development of novel strategies for more effective CMV vaccines or antiviral immunotherapies.

Keywords: Antibodies; Cytomegalovirus; Fc receptor; Monocytes.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / immunology
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / prevention & control
  • Herpesviridae Infections / immunology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Monocytes / immunology
  • Muromegalovirus* / immunology
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism
  • Receptors, IgG* / immunology
  • Receptors, IgG* / metabolism

Substances

  • Receptors, IgG
  • Antibodies, Viral
  • Fcgr4 protein, mouse
  • Antibodies, Neutralizing
  • Receptors, Fc
  • Fcgr1 protein, mouse