CD8α+ dendritic cells (DCs) are crucial components of the antiviral response in mice, priming virus-specific cytotoxic T lymphocytes (CTLs). They are also the principal mediator of cross-presentation in vivo. So, Schulz et al. proposed that CD8α+ DCs that are cross-presenting antigens from phagocytosed virally infected cells must receive a signal to favour cross-priming. Given that viral infection is associated with the generation of double-stranded RNA (dsRNA) and that CD8α+ DCs express the dsRNA receptor TLR3, they set out to investigate whether TLR3 might provide this signal.
CD8α+ DCs cultured in the presence of Vero cells (a primate cell line) that had been loaded with synthetic dsRNA (polyinosinic–polycytidylic acid, polyI:C) and exposed to ultraviolet light to induce cell death phagocytosed the polyI:C-loaded Vero cells. This induced increased cell-surface expression of CD40, CD80 and CD86, and increased production of inflammatory cytokines, including interleukin-6. By contrast, mock-treated cells did not induce activation of the CD8α+ DCs. Similar uptake and activation was observed when CD8α+ DCs were cultured in the presence of Vero cells infected with either encephalomyocarditis virus or Semliki Forest virus (SFV). Phagocytosis and phagosomal acidification were essential for the polyI:C-loaded Vero cells to induce CD8α+ DC activation, and further studies showed that TLR3 was also required for activation induced by either infected or polyI:C-loaded Vero cells.
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