Multi‐functional plasmacytoid dendritic cells redistribute to gut tissues during simian immunodeficiency virus infection

Summary The objective of this study was to determine the systemic effects of chronic simian immunodeficiency virus ( SIV ) infection on plasmacytoid dendritic cells (p DC s). p DC s play a critical role in antiviral immunity, but current data are conflicting on whether p DC s inhibit HIV / SIV replication, or, alternatively, contribute to chronic immune activation and disease. Furthermore, previous p DC studies have been complicated by incomplete descriptions of generalized depletion during HIV / SIV infection, and the effects of infection on p DC s outside peripheral blood remain unclear. In scheduled‐sacrifice studies of naive and chronically SIV ‐infected rhesus macaques we evaluated the distribution and functionality of p DC s in multiple tissues using surface and intracellular polychromatic flow cytometry. As previously observed, p DC s were reduced in peripheral blood and spleens, but were also depleted in non‐lymphoid organs such as the liver. Interestingly, pDC s accumulated up to fourfold in jejunum, colon and gut‐draining lymph nodes, but not in peripheral lymph nodes. Most unexpectedly, SIV infection induced a multi‐functional interferon‐α, tumour necrosis factor‐α, and macrophage inflammatory protein‐1β cytokine secretion phenotype, whereas in normal animals these were generally distinct and separate functions. Herein we show a systemic redistribution of p DC s to gut tissues and gut‐draining lymph nodes during chronic SIV infection, coupled to a novel multi‐functional cytokine‐producing phenotype. While p DC accumulation in the mucosa could aid in virus control, over‐production of cytokines from these cells could also contribute to the increased immune activation in the gut mucosa commonly associated with progressive lentivirus infections.