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in Peripheral Blood Dendritic Cells by Enveloped RNA and DNA Viruses1
*
University of Medicine and Dentistry of New Jersey–New Jersey Medical School and
The Graduate School of Biomedical Sciences, Newark, NJ 07103
Peripheral blood dendritic cells (DC) produce IFN-
in response
to challenge by many enveloped viruses including herpes simplex virus
(HSV) and HIV, whereas Sendai virus predominantly stimulates IFN-
production by monocytes. Glycosylated viral envelope proteins are known
to be important for the induction of IFN-. In this study we
demonstrate that stimulation of IFN- synthesis by HSV is inhibited
by a number of monosaccharides, including fucose,
N-acetylglucosamine, and
N-acetylgalactosamine as well as the yeast
polysaccharide mannan, supporting a role for lectin(s) in the IFN-
stimulation pathway. Furthermore, antiserum to the mannose receptor
(MR) also inhibited HSV, vesicular stomatitis virus, and HIV-induced
IFN- production, but failed to inhibit the IFN- induced by Sendai
virus. We further demonstrated that freshly isolated blood DC and
IFN--producing cells responding to HSV stimulation express the MR.
This study therefore implicates the MR as an important receptor for the
nonspecific recognition of enveloped viruses by DC and the subsequent
stimulation of IFN- production by these viruses. Thus, the MR
probably serves as a critical link between innate and adaptive immunity
to viruses, especially given the role of the MR in Ag capture by DC and
the importance of IFN- in shaping immunity.
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