A Protective Role for Interleukin-1 Signaling during Mouse Adenovirus Type 1-Induced Encephalitis
| Autor: | Luiza A. Castro-Jorge, Oded Foreman, Kelly E. Carnahan, Carla D. Pretto, Katherine R. Spindler, Asa B. Smith |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Transcription Genetic medicine.medical_treatment Adenoviridae Infections Immunology Endosomes Virus Replication Microbiology Permeability Pathogenesis 03 medical and health sciences Mastadenovirus Mice 0302 clinical medicine Interferon Virology medicine Animals Mice Knockout biology Viral encephalitis Toll-Like Receptors Brain medicine.disease Immunity Innate 030104 developmental biology Cytokine Viral replication Blood-Brain Barrier Insect Science Knockout mouse Host-Pathogen Interactions biology.protein Cytokines Encephalitis Pathogenesis and Immunity Inflammation Mediators 030217 neurology & neurosurgery medicine.drug Interleukin-1 Signal Transduction |
| Zdroj: | Journal of virology. 91(4) |
| ISSN: | 1098-5514 |
| Popis: | Interleukin-1β (IL-1β), an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor ( Il1r1 −/− mice). Il1r1 −/− mice demonstrated reduced survival, greater disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokine and chemokine levels than control C57BL/6J mice. We also examined infections of mice defective in IL-1β production ( Pycard −/− mice) and mice defective in trafficking of Toll-like receptors to the endosome ( Unc93b1 −/− mice). Pycard −/− and Unc93b1 −/− mice showed lower survival (similar to Il1r1 −/− mice) than control mice but, unlike Il1r1 −/− mice, did not have increased brain viral loads or BBB disruption. Based on the brain cytokine levels, MAV-1-infected Unc93b1 −/− mice had a very different inflammatory profile from infected Il1r1 −/− and Pycard −/− mice. Histological examination demonstrated pathological findings consistent with encephalitis in control and knockout mice; however, intranuclear viral inclusions were seen only in Il1r1 −/− mice. A time course of infection of control and Il1r1 −/− mice evaluating the kinetics of viral replication and cytokine production revealed differences between the mouse strains primarily at 7 to 8 days after infection, when mice began succumbing to MAV-1 infection. In the absence of IL-1 signaling, we noted an increase in the transcription of type I interferon (IFN)-stimulated genes. Together, these results indicate that IL-1 signaling is important during MAV-1 infection and suggest that, in its absence, increased IFN-β signaling may result in increased neuroinflammation. IMPORTANCE The investigation of encephalitis pathogenesis produced by different viruses is needed to characterize virus and host-specific factors that contribute to disease. MAV-1 produces viral encephalitis in its natural host, providing a good model for studying factors involved in encephalitis development. We investigated the role of IL-1 signaling during MAV-1-induced encephalitis. Unexpectedly, the lack of IL-1 signaling increased the mortality and inflammation in mice infected with MAV-1. Also, there was an increase in the transcription of type I IFN-stimulated genes that correlated with the observed increased mortality and inflammation. The findings highlight the complex nature of encephalitis and suggests that IL-1 has a protective effect for the development of MAV-1-induced encephalitis. |
| Databáze: | OpenAIRE |
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