A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques.

Abstract

BACKGROUND: The mechanism for loss of myeloid dendritic cells (mDCs) from the circulation in HIV-infected individuals and its relationship to disease progression is not understood. METHODS: A longitudinal analysis of the mDC response in blood and lymph nodes during the first 12 weeks of infection was performed in a cohort of SIVmac251-infected rhesus macaques with different disease outcomes. RESULTS: Monkeys that rapidly progressed to disease or had long-term stable infection had significant losses or increases, respectively, in blood mDCs that were inversely correlated with virus load at set-point. The loss of mDCs from progressor animals was associated with evidence of an increase in CCR7/CCL19-dependent mDC recruitment to lymph nodes and an increase in mDC apoptosis. CONCLUSIONS: mDC recruitment to and death within inflamed lymph nodes may contribute to disease progression in SIV infection, whereas mobilization without increased recruitment to lymph nodes may promote disease control.