AUTHOR=Elwy Abdelrahman , Dhiman Swati , Abdelrahman Hossam , Specht Julia , Christ Theresa Charlotte , Falkenstein Julia , Kaur Harpreet , Holnsteiner Lisa , Lang Judith , Mack Matthias , Nimmerjahn Falk , Hansen Wiebke , Lang Karl Sebastian 

TITLE=Patrolling monocytes mediate virus neutralizing IgG effector functions: beyond neutralization capacity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1600056

DOI=10.3389/fimmu.2025.1600056

ISSN=1664-3224

ABSTRACT=Neutralizing antibodies (nAbs) are pivotal in developing fast, broadly protective therapeutics against novel pandemic viruses. Despite their well-known direct neutralization capacity, their effector mechanisms via Fc receptors remain poorly understood. Identifying the types of effector cells engaged in antibody-mediated effector functions is essential for regulating their activities. Using the lymphocytic choriomeningitis virus (LCMV), we show that nAbs obtained from immune sera or monoclonal LCMV-specific nAbs show dependency on Fc receptors. We demonstrate that therapy with nAbs is highly protective in the presence of patrolling monocytes. These monocytes bind nAbs primarily via FcγRIV, targeting virus-infected cells, and thereby limiting virus propagation. Depleting patrolling monocytes or blocking FcγRIV resulted in a substantial loss of virus control by nAbs, indicating the pivotal role of patrolling monocytes in the antiviral activity of these antibodies. In conclusion, our findings highlight that, alongside direct neutralization, nAbs primarily exert their effects through the involvement of patrolling monocytes.