Protection from RNA and DNA viruses by IL-32
| Autor: | Jarod A. Zepp, Charles A. Dinarello, Marcel F. Nold, Claudia A. Nold-Petry |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Herpesvirus 2
Human Immunology Biology Virus Vesicular stomatitis Indiana virus Proinflammatory cytokine Cell Line Immune system Cytopathogenic Effect Viral Chlorocebus aethiops Immunology and Allergy Gene silencing Animals Humans Vero Cells Herpes Genitalis L-Lactate Dehydrogenase Interleukins Health aging / healthy living Pathogenesis and modulation of inflammation [IGMD 5] RNA DNA virus Viral Load Virology Molecular biology Cell culture Vero cell Endothelium Vascular Inflammation Mediators Vesicular Stomatitis |
| Zdroj: | Journal of Immunology, 186, 7, pp. 4110-8 Journal of Immunology, 186, 4110-8 |
| ISSN: | 0022-1767 |
| Popis: | Several studies have documented a proinflammatory role for IL-32, which induces IL-1α, IL-1β, IL-6, TNF, and chemokines via NF-κB, p38MAPK, and AP-1. However, IL-32 also participates in the responses to infection with viruses such as HIV-1 and influenza. In this study, we explored these antiviral properties of IL-32. Vital staining assays demonstrated that low concentrations (5–10 ng/ml) of rIL-32γ protected epithelial WISH cells from vesicular stomatitis virus-induced cell death. By lactate dehydrogenase assays, treatment with IL-32γ resulted in a 3- to 4-fold decrease in viral load. Specific silencing of IL-32 revealed that the antiviral responses triggered by the synthetic analogs of ssRNA viruses (polyuridine) and dsRNA viruses (polyinosinic-polycytidylic acid) were significantly weaker (2- to 3-fold more virus) in WISH cells in the absence of IL-32. Importantly, we discovered that the polyinosinic-polycytidylic acid-induced increase in production of IFN-α in human PBMC was nearly completely abolished when IL-32 was silenced. Moreover, we observed that IL-32 antagonizes the DNA virus HSV-2 in epithelial Vero cells as well as in human umbilical cord endothelial cells, as production of HSV-2 increased 8-fold upon silencing of IL-32 (p < 0.001). Mechanistically, we found that IL-32 used the PKR-eIF-2α as well as the MxA antiviral pathways. Unexpectedly, a considerable part of the antiviral properties of IL-32 was not dependent on IFNs; specific blockade of IFN activity reduced the antiviral properties of IL-32 only moderately. In conclusion, these data suggest a central role for IL-32 in the immune response to RNA and DNA viruses, which may be exploitable for clinical use in the future. |
| Databáze: | OpenAIRE |
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