Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance.
| Autor: | Dunagan MM; Emerging Virus Immunity Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Dábilla N; Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., McNinch C; Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Brenchley JM; Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Dolan PT; Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Fox JM; Emerging Virus Immunity Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 24. Date of Electronic Publication: 2024 Jul 24. |
| DOI: | 10.1101/2024.07.23.604823 |
| Abstrakt: | Mayaro virus (MAYV) is an emerging arbovirus. Previous studies have shown antibody Fc effector functions are critical for optimal monoclonal antibody-mediated protection against alphaviruses; however, the requirement of Fc gamma receptors (FcγRs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcγRs (FcRγ -/- ) developed prolonged clinical disease with more virus in joint-associated tissues. Viral clearance was associated with anti-MAYV cell surface binding rather than neutralizing antibodies. Lack of Fc-FcγR engagement increased the number of monocytes through chronic timepoints. Single cell RNA sequencing showed elevated levels of pro-inflammatory monocytes in joint-associated tissue with increased MAYV RNA present in FcRγ -/- monocytes and macrophages. Transfer of FcRγ -/- monocytes into wild type animals was sufficient to increase virus in joint-associated tissue. Overall, this study suggests that engagement of antibody Fc with activating FcγRs promotes protective responses during MAYV infection and prevents monocytes from being potential targets of infection. |
| Databáze: | MEDLINE |
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