Melanomacrophages exhibit FDC-like features: aquatic reovirus induces melanomacrophage death to suppress antibody responses

Abstract

Genotype II grass carp reovirus (GCRV-II)-caused grass carp hemorrhagic disease severely restricts aquaculture, yet its adaptive immune evasion mechanism remains unclear. In mammals, follicular dendritic cells (FDCs) act as the core antigen-presenting cells that drive germinal center (GC)-mediated antibody responses; however, the core antigen-presenting cells within teleost GC-like structures are undefined, and whether aquatic viruses target these cells to evade host antibody responses remains elusive. Here, we confirmed the presence of functional GC-like structures in immunized grass carp spleen and identified melanomacrophages (MMφs) as FDC-like cells that capture and present intact antigens. Importantly, GCRV-II infection significantly impaired GC-like structure formation and suppressed antibody responses. Mechanistically, GCRV-II infects grass carp MMφs, inducing coordinated apoptosis and gasdermin Ea/gasdermin Eb (GSDMEa/GSDMEb)-dependent pyroptosis. This process promoted GCRV-II replication and dissemination, depleted MMφ populations, and ultimately prevented GC-like structure formation. This study clarifies the cellular composition of GC-like structures in ectothermic vertebrates, unveils an unreported aquatic viral immune evasion strategy, and provides key targets for the rational design of teleost vaccines.