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Updated: Jun 16, 2025
Use of a Monocyte Monolayer Assay to Evaluate Fcγ Receptor-mediated Phagocytosis
Published on: January 2, 2017
Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance
Megan M Dunagan1, Nathânia Dábilla2, Colton McNinch3
1Emerging Virus Immunity Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Abstract:
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.
Insights
Engaging Fc gamma receptors (FcγRs) with antibody Fc is crucial for controlling Mayaro virus (MAYV) infection. Blocking FcγRs prolongs disease and increases viral load in tissues, highlighting FcγR
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Mayaro virus (MAYV) is an emerging arbovirus with significant public health implications.
- Antibody Fc effector functions are known to be critical for protection against alphaviruses, but their role in natural MAYV infection is unclear.
- Fc gamma receptors (FcγRs) mediate antibody effector functions.
Purpose of the Study:
- To investigate the role of activating Fc gamma receptors (FcγRs) in protection against Mayaro virus (MAYV) during natural infection.
- To determine the impact of FcγR deficiency on disease progression, viral clearance, and immune cell responses in MAYV-infected mice.
Main Methods:
- Utilized FcRγ knockout mice (FcRγ-/-) lacking activating FcγRs and wild-type controls.
- Assessed clinical disease, viral load in joint-associated tissues, and antibody functions (neutralizing vs. cell surface binding).
- Employed single-cell RNA sequencing to analyze immune cell populations, particularly monocytes and macrophages, in affected tissues.
Main Results:
- Mice lacking activating FcγRs (FcRγ-/-) exhibited prolonged clinical disease and increased viral burden in joint-associated tissues.
- Viral clearance correlated with anti-MAYV cell surface binding antibodies, not neutralizing antibodies.
- FcRγ-/- mice showed an increased number of monocytes, with elevated pro-inflammatory monocytes and increased MAYV RNA in monocytes and macrophages.
- Transfer of FcRγ-/- monocytes into wild-type animals exacerbated viral load in joint tissues.
Conclusions:
- Engagement of antibody Fc with activating FcγRs is essential for protective immune responses during Mayaro virus infection.
- FcγR signaling prevents monocytes from becoming targets for MAYV replication, thereby controlling viral spread.
- This study underscores the importance of FcγR-mediated effector functions in combating arboviral infections like MAYV.
