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Vliv malých DNA virů na funkci plasmacytoidních dendritických buněk / Effect of small DNA viruses on function of plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDC) are a highly specialized subset of immune cells that sense viral nucleic acids by endosomal toll-like receptors 7 and 9 (TLR7/9). Activation of TLR7/9 leads to the production of type I interferons (IFN-I). Moreover, pDC contribute to the antiviral response by presenting viral antigens to T lymphocytes and link innate and adaptive immunity. pDC need to be properly regulated in order to limit excessive production of IFN-I that is associated with autoimmune diseases. Therefore, pDC possess a battery of regulatory receptors (RR) that limit TLR7/9-mediated cytokine production. This thesis focuses on the mechanism of RR-mediated inhibition of IFN-I production in pDC and explores interactions between pDC and two enveloped viruses, that possess the ability to hijack RR in pDC: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). We showed, that MEK-ERK signaling pathway plays an active role in RR-mediated inhibition of IFN-I in pDC. Our results indicate that in line with other studies of our group, pharmacological targeting of MEK1/2-ERK signaling could be a strategy to re-establish immunogenic activity of pDC. Then, we investigated whether antiretroviral therapy (ART) in a cohort of 21 treatment-naive chronic HIV-infected patients has restored the number and...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:452897
Date January 2021
CreatorsJanovec, Václav
ContributorsHirsch, Ivan, Růžek, Daniel, Filipp, Dominik
Source SetsCzech ETDs
LanguageCzech
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/doctoralThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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