RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis
Respiratory syncytial virus (RSV) is a significant public health concern. Nearly all children are infected by two years of age, and severe infection often results in hospitalization. There is no vaccine for RSV, and previous attempts have resulted in increased disease severity in immunized children once they were exposed to the virus. Therefore, a better understanding of how RSV directs the immune response is needed. In this study, we found that the protein KDM5B regulates an epigenetic mechanism that directs the immune response to RSV. KDM5B suppressed the activation of key antiviral signals in dendritic cells, and inhibition of KDM5B led to gene activation and increased antiviral function. This correlated with decreased pathology in the lungs. Therefore, our data suggest that new attempts at designing a vaccine should consider the effects of vaccination on dendritic cells, and should consider strategies that will increase antiviral signals from dendritic cells.
Vyšlo v časopise:
RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004978
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004978
Souhrn
Respiratory syncytial virus (RSV) is a significant public health concern. Nearly all children are infected by two years of age, and severe infection often results in hospitalization. There is no vaccine for RSV, and previous attempts have resulted in increased disease severity in immunized children once they were exposed to the virus. Therefore, a better understanding of how RSV directs the immune response is needed. In this study, we found that the protein KDM5B regulates an epigenetic mechanism that directs the immune response to RSV. KDM5B suppressed the activation of key antiviral signals in dendritic cells, and inhibition of KDM5B led to gene activation and increased antiviral function. This correlated with decreased pathology in the lungs. Therefore, our data suggest that new attempts at designing a vaccine should consider the effects of vaccination on dendritic cells, and should consider strategies that will increase antiviral signals from dendritic cells.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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