Nuclear receptor REV-ERBα mediates circadian sensitivity to mortality in murine vesicular stomatitis virus-induced encephalitis
| Autor: | Ilia N. Karatsoreos, Karen Bulloch, Marina Moskalenko, Kaitlyn H. Hajdarovic, Bruce S. McEwen, Khatuna Gagnidze |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Chemokine viruses medicine.medical_treatment Circadian clock CLOCK Proteins Gene Expression Mice Transgenic Adaptive Immunity Monocytes Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system Zeitgeber medicine Animals Circadian rhythm Mortality Multidisciplinary biology Vesiculovirus Biological Sciences biology.organism_classification Circadian Rhythm Up-Regulation Mice Inbred C57BL 030104 developmental biology Cytokine Vesicular stomatitis virus Nuclear Receptor Subfamily 1 Group D Member 1 Immunology biology.protein Cytokines Encephalitis 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences. 113:5730-5735 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Certain components and functions of the immune system, most notably cytokine production and immune cell migration, are under circadian regulation. Such regulation suggests that circadian rhythms may have an effect on disease onset, progression, and resolution. In the vesicular stomatitis virus (VSV)-induced encephalitis model, the replication, caudal penetration, and survivability of intranasally applied VSV depends on both innate and adaptive immune mechanisms. In the current study, we investigated the effect of circadian time of infection on the progression and outcome of VSV-induced encephalitis and demonstrated a significant decrease in the survival rate in mice infected at the start of the rest cycle, zeitgeber time 0 (ZT0). The lower survival rate in these mice was associated with higher levels of circulating chemokine (C-C motif) ligand 2 (CCL2), a greater number of peripherally derived immune cells accumulating in the olfactory bulb (OB), and increased production of proinflammatory cytokines, indicating an immune-mediated pathology. We also found that the acrophase of molecular circadian clock component REV-ERBα mRNA expression in the OB coincides with the start of the active cycle, ZT12, when VSV infection results in a more favorable outcome. This result led us to hypothesize that REV-ERBα may mediate the circadian effect on survival following VSV infection. Blocking REV-ERBα activity before VSV administration resulted in a significant increase in the expression of CCL2 and decreased survival in mice infected at the start of the active cycle. These data demonstrate that REV-ERBα-mediated inhibition of CCL2 expression during viral-induced encephalitis may have a protective effect. |
| Databáze: | OpenAIRE |
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