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

Author:

Bootz Anna1,Reuter Nina1,Nimmerjahn Falk2ORCID,Britt William J.3,Mach Michael1,Winkler Thomas H.4

Affiliation:

1. Institute of Clinical and Molecular Virology Universitätsklinikum Erlangen Friedrich‐Alexander University Erlangen‐Nürnberg Erlangen Germany

2. Division of Genetics Department Biology Friedrich‐Alexander University Erlangen‐Nürnberg Erlangen Germany

3. Departments of Pediatrics Microbiology and Neurobiology Children's Hospital of Alabama School of Medicine University of Alabama Birmingham Alabama USA

4. Division of Genetics Department Biology Nikolaus‐Fiebiger‐Center of Molecular Medicine Friedrich‐Alexander University Erlangen‐Nürnberg Erlangen Germany

Abstract

AbstractHuman 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.

Funder

Deutsche Forschungsgemeinschaft

National Science Foundation

Publisher

Wiley

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