Infectious and inactivated foot-and-mouth disease virus serotypes A/ARG/2001 and O1 Campos/Bra/58 differentially affect bovine afferent lymph dendritic cells

Introduction Dendritic cells (DCs) are central to the initiation of adaptive immune responses by bridging innate and adaptive immunity through antigen presentation to naïve T cells. Current vaccines against Foot-and-Mouth Disease (FMD) rely on inactivated virus, although infectious and inactivated forms of FMDV can differentially modulate immune function. While these effects have been studied in murine DCs, their impact on bovine dendritic cells remains poorly understood. This study evaluated how antigen form and serotype affect bovine afferent lymph dendritic cells (ALDCs). Methods ALDCs collected from bovine lymph, a physiologically relevant migrating DC population, were exposed to infectious or inactivated FMDV serotypes A/ARG/2001 (A2001) and O1 Campos/Bra/58 (O1C), both included in the commercial vaccine used in Argentina. The expression of MHC class II and the co-stimulatory molecules CD40 and CD86, apoptosis, IL-12 production, and lymphocyte proliferation in co-culture assays were evaluated. Viral progeny production and expression of the non-structural protein 3ABC were also assessed. Results Infectious A2001 downregulated MHC class II, CD40, and CD86 expression and increased apoptosis, whereas infectious O1C selectively downregulated MHC class II without affecting ALDC viability. In contrast, inactivated viruses from both serotypes upregulated CD40 and CD86 expression, induced IL-12 production, and promoted lymphocyte proliferation in co-culture assays. No infectious progeny was detected in lymph cells following exposure to infectious virus, although expression of the non-structural protein 3ABC was observed in ALDCs exposed to infectious A2001. Discussion These findings provide insight into how antigen form and serotype modulate dendritic cell function in cattle, contributing to a better understanding of the immunological basis for FMDV vaccination strategies in livestock.