IL-4-mediated monocyte differentiation modulates CD163 expression and PRRSV infection.

Host immune status critically influences susceptibility to viral infections; however, the impact of cytokine-driven innate immune differentiation on viral permissiveness remains poorly understood. Here, we investigated whether IL-4-mediated monocyte differentiation modulates porcine reproductive and respiratory syndrome virus (PRRSV) infection. Porcine monocytes were differentiated in the presence of GM-CSF with or without IL-4 to generate monocyte-derived cells (MDCs). Notably, PRRSV replication was significantly higher in MDCs generated without IL-4 compared to those differentiated in the presence of IL-4, which was strongly associated with increased CD163 expression. Consistently, CD163 expression was downregulated in an IL-4-dependent manner. Following PRRSV infection, MDCs differentiated without IL-4 exhibited reduced TNF-α production but elevated IL-6 and IL-10 levels. In addition, MDCs generated without IL-4 showed increased expression of CD80 and SLA-1 and significantly impaired the proliferation of autologous CD8+ T cells compared to MDCs differentiated with IL-4. In vivo analysis further revealed a negative correlation between plasma IL-4 levels and CD163 expression in alveolar MDCs of PRRSV-infected pigs, which was associated with increased proportions of CD8+ T cells. Collectively, these findings suggest that IL-4-mediated innate immune programming regulates cellular permissiveness to PRRSV infection and may contribute to protective host immune responses.