BioProject

Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma, SSc), with increased expression of IFN-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. More...

Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma, SSc), with increased expression of IFN-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. Recently, we found that EBV is deregulated in SSc with abnormal expression of viral lytic-genes in PBMCs and skin. Since monocytes/macrophages are involved in innate immune recognition of EBV/lytic infection, we sought to determine whether EBV might contribute to their activation in SSc. In this study, using recombinant-EBV we infected monocytes from SSc and healthy donors (HDs), we found that viral replication is essential for inducing the expression of TLR8 in EBV-infected primary monocytes. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were up-regulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally-induced-TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral lytic-mRNA and -proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. Overall design: Four dcSSc monocytes tested positive for EBV lytic genes were compared to age-matched monocytes from HDs. Less...