TNF-α and IL-10 differentially modulate apoptosis during PRRSV-1 infection of bone marrow-derived dendritic cells

Porcine reproductive and respiratory syndrome virus (PRRSV) modulates host immune responses, including apoptotic pathways, during infection. This study examined the role of TNF-α and IL-10 in regulating apoptosis during PRRSV-1 infection of bone marrow-derived dendritic cells (BMDCs), using four isolates with distinct cytokine profiles: 3262 (TNF-α ⁺ /IL-10 ⁺ ), 3249 (TNF-α ⁺ /IL-10 ^- ), 2988 (TNF-α ^- /IL-10 ⁺ ), and 3267 (TNF-α ^- /IL-10 ^- ). Early after infection (≤ 24 hpi), infected cells were predominantly non-apoptotic; by 48 hpi, apoptotic bystander cells increased markedly, consistent with a bystander apoptotic process. Neutralizing TNF-α in TNF-α-inducing isolates (3262, 3249) increased the proportion of infected cells and reduced bystander apoptosis, suggesting an antiviral role for TNF-α at the cellular level. In contrast, IL-10 blockade in IL-10-inducing isolates (3262, 2988) increased non-apoptotic infected cells without altering overall infection frequency, suggesting IL-10 modulates apoptotic progression in infected cells. Collectively, these data indicate that TNF-α and IL-10 differentially modulate apoptotic outcomes during PRRSV-1 infection in an isolate-dependent manner.