Abstract
BACKGROUND: During progressive simian immunodeficiency virus (SIV) infection, the ability of innate mononuclear phagocytes to function when responding to the invading pathogen has yet to be determined. METHODS: We generated single-stranded RNA (ssRNA) oligonucleotides from the infecting strain of virus and utilized them to stimulate mononuclear phagocytes from blood and lymph nodes of naïve and SIVmac251-infected rhesus macaques. RESULTS: Soon after infection and continuing through to chronic disease, plasmacytoid dendritic cells (pDC), monocytes, and macrophages from SIV-infected macaques were less able to produce pro-inflammatory cytokines after exposure to virus-derived toll-like receptor (TLR) agonists. In contrast, myeloid dendritic cells (mDC) became hyper-responsive during acute and stable chronic infection. CONCLUSIONS: Plasmacytoid dendritic cells, monocytes, and macrophages may not instigate continued immune activation by recognizing the single-stranded RNA from SIV as they are left dysfunctional after infection. Conversely, mDC functionality may be beneficial as their hyper-responsiveness is related to slowed disease progression.