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

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Host immune status significantly impacts viral infection susceptibility.
• The role of cytokine-driven innate immune cell differentiation in viral permissiveness is not well understood.

Purpose of the Study:

• To investigate the effect of IL-4-mediated monocyte differentiation on porcine reproductive and respiratory syndrome virus (PRRSV) infection.
• To understand how IL-4 influences innate immune cell programming and viral permissiveness.

Main Methods:

• Porcine monocytes were differentiated into monocyte-derived cells (MDCs) with or without IL-4, using GM-CSF.
• PRRSV replication, CD163 expression, cytokine production (TNF-α, IL-6, IL-10), and T cell proliferation were analyzed.
• In vivo studies correlated plasma IL-4 levels with alveolar MDC CD163 expression and CD8+ T cell proportions in PRRSV-infected pigs.

Main Results:

• PRRSV replication was significantly higher in MDCs differentiated without IL-4, associated with increased CD163 expression.
• IL-4 downregulated CD163 expression in an IL-4-dependent manner.
• MDCs without IL-4 showed reduced TNF-α but elevated IL-6/IL-10, increased CD80/SLA-1, and impaired CD8+ T cell proliferation.
• In vivo, lower IL-4 correlated with higher CD163 and fewer CD8+ T cells in PRRSV-infected pigs.

Conclusions:

• IL-4-mediated innate immune programming regulates cellular permissiveness to PRRSV.
• IL-4 may contribute to protective host immune responses against PRRSV infection by modulating monocyte differentiation and function.