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

## TL;DR

This study shows that antibodies not only neutralize viruses directly but also rely on patrolling monocytes to help control viral spread through Fc receptor interactions.

## Contribution

The study identifies patrolling monocytes and FcγRIV as key mediators of neutralizing antibody effector functions in antiviral immunity.

## Key findings

- Patrolling monocytes are essential for the antiviral activity of neutralizing antibodies.
- Neutralizing antibodies bind to patrolling monocytes via FcγRIV to target infected cells.
- Blocking FcγRIV or depleting patrolling monocytes reduces the effectiveness of neutralizing antibodies.

## 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.