THE MANNOSE RECEPTOR MEDIATES INDUCTION OF IFN-ALPHA IN PERIPHERAL-BLOOD DENDRITIC CELLS BY ENVELOPED RNA AND DNA VIRUSES

Peripheral blood dendritic cells (DC) produce IFN-alpha in response to challenge by many enveloped viruses including herpes simplex virus (H SV) and HIV, whereas Sendai virus predominantly stimulates IFN-alpha p roduction by monocytes. Glycosylated viral envelope proteins are known to be important for the induction of IFN-alpha. In this study we demo nstrate that stimulation of IFN-alpha synthesis by HSV is inhibited by a number of monosaccharides, including fucose, N-acetylglucosamine, a nd N-acetylgalactosamine as well as the yeast polysaccharide mannan, s upporting a role for lectin(s) in the IFN-alpha stimulation pathway. F urthermore, antiserum to the mannose receptor (MR) also inhibited HSV, vesicular stomatitis virus, and HIV-induced IFN-alpha production, but failed to inhibit the IFN-alpha induced by Sendai virus. We further d emonstrated that freshly isolated blood DC and IFN-alpha-producing cel ls responding to HSV stimulation express the MR. This study therefore implicates the MR as an important receptor for the nonspecific recogni tion of enveloped viruses by DC and the subsequent stimulation of IFN- alpha production by these viruses. Thus, the MR probably serves as a c ritical link between innate and adaptive immunity to viruses, especial ly given the role of the MR in Ag capture by DC and the importance of IFN-alpha in shaping immunity.