Innate Immune Mechanisms Triggered by SARS-CoV-2 Virus-Like Particles: Role of Antibody Opsonization.

The rapid spread of SARS-CoV-2 highlighted the need to understand the nature of innate immune signaling. We used virus-like particles (VLPs) composed of SARS-CoV-2 structural proteins, spike, envelope, membrane, and nucleocapsid, mimicking the virus to study macrophage responses to VLPs and their immune complexes (ICs), which represent antibody-opsonized particles cleared by innate immune cells. We assessed antibody affinity and IC properties using quartz crystal microbalance with dissipation (QCM-D). Human THP-1-derived macrophages treated with VLPs or ICs showed inflammatory activation, including inflammasome signaling, chemokine receptor expression, and antigen-presentation-related markers CD86/CD83. Notably, ICs triggered lower chemokine secretion but similar TNF-α release and enhanced IL-1β production, with increased ASC protein expression in some cases. These findings reveal distinct macrophage responses to viral antigens vs ICs, emphasizing IC-driven inflammasome activation during SARS-CoV-2 infection, independent of chemokine secretion profiles.