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The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA
M C Milone1, P Fitzgerald-Bocarsly
1University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.
Abstract:
Peripheral blood dendritic cells (DC) produce IFN-alpha in response to challenge by many enveloped viruses including herpes simplex virus (HSV) and HIV, whereas Sendai virus predominantly stimulates IFN-alpha production by monocytes. Glycosylated viral envelope proteins are known to be important for the induction of IFN-alpha. In this study we demonstrate that stimulation of IFN-alpha 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-alpha stimulation pathway. Furthermore, 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 demonstrated that freshly isolated blood DC and IFN-alpha-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-alpha 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-alpha in shaping immunity.
Insights
Peripheral blood dendritic cells (DCs) use the mannose receptor (MR) to recognize enveloped viruses like HSV and HIV, stimulating crucial IFN-alpha production. This receptor acts as a key link between innate and adaptive immunity against viral infections.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Peripheral blood dendritic cells (DCs) produce interferon-alpha (IFN-alpha) in response to various enveloped viruses, including herpes simplex virus (HSV) and human immunodeficiency virus (HIV).
- Glycosylated viral envelope proteins are recognized as significant inducers of IFN-alpha production.
- Monocytes, unlike DCs, predominantly stimulate IFN-alpha production in response to Sendai virus.
Purpose of the Study:
- To investigate the role of lectins, specifically the mannose receptor (MR), in the IFN-alpha stimulation pathway induced by enveloped viruses in dendritic cells.
- To elucidate the mechanism by which dendritic cells recognize and respond to viral challenges, leading to IFN-alpha production.
Main Methods:
- Inhibition assays using monosaccharides (fucose, N-acetylglucosamine, N-acetylgalactosamine) and mannan to assess the role of lectins in HSV-induced IFN-alpha synthesis.
- Utilizing antiserum against the mannose receptor (MR) to evaluate its role in IFN-alpha production stimulated by HSV, vesicular stomatitis virus, and HIV.
- Immunological assays to detect the expression of the MR on freshly isolated blood DCs and IFN-alpha-producing cells stimulated by HSV.
Main Results:
- HSV-induced IFN-alpha synthesis was inhibited by specific monosaccharides and mannan, suggesting lectin involvement.
- Antiserum to the MR inhibited IFN-alpha production induced by HSV, vesicular stomatitis virus, and HIV, but not by Sendai virus.
- Freshly isolated blood DCs and IFN-alpha-producing cells stimulated by HSV were found to express the MR.
Conclusions:
- The mannose receptor (MR) is implicated as a critical receptor for the non-specific recognition of enveloped viruses by dendritic cells.
- MR engagement by viruses leads to the subsequent stimulation of IFN-alpha production by DCs.
- The MR plays a vital role in linking innate and adaptive immunity to viruses, facilitating antigen capture by DCs and leveraging IFN-alpha's immunomodulatory functions.