Modulation of plasmacytoid dendritic cell function: role of immunoreceptors TIM-3 and BDCA-2

• Název práce v češtině: Modulace funkce plazmacytoidních dendritických buněk: role immunoreceptorů TIM-3 a BDCA-2
• Název v anglickém jazyce: Modulation of plasmacytoid dendritic cell function: role of immunoreceptors TIM-3 and BDCA-2
• Klíčová slova: HIV-1, plasmacytoidní dendritické buňky (pDCs), Toll-like receptor 7 a 9 (TLR7/TLR9), regulačně/inhibiční imunoreceptory BDCA-2 a TIM-3, interferon typu I (IFN-I), inhibitory kináz SYK a MEK-ERK, restrikce HIV-1 v pDCs, viremičtí a neviremičtí pacienti infikovaní HIV-1, strategie antiretrovirové terapie
• Klíčová slova anglicky: HIV-1, plasmacytoid dendritic cells (pDCs), Toll-like receptor 7 and 9 (TLR7/TLR9), regulatory/inhibitory immunoreceptors BDCA-2 and TIM-3, type I interferon (IFN-I), SYK and MEK-ERK kinase inhibitors, HIV-1 restriction in pDCs, viremic and aviremic HIV-1 infected individuals, strategies for anti-HIV-1 therapy
• Akademický rok vypsání: 2014/2015
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Katedra genetiky a mikrobiologie (31-140)
• Vedoucí / školitel: prof. RNDr. Ivan Hirsch, CSc.
• Řešitel: skrytý - zadáno vedoucím/školitelem
• Datum přihlášení: 05.11.2014
• Datum zadání: 05.11.2014
• Datum odevzdání elektronické podoby: 08.04.2021
• Datum proběhlé obhajoby: 17.06.2021
• Oponenti: RNDr. Šárka Němečková, DrSc.
• Konzultanti: Mgr. Kateřina Trejbalová, Ph.D.

Předběžná náplň práce v anglickém jazyce

The preliminary aim of my thesis was to study and evaluate the role of regulatory immunoreceptors (RRs) present in the cell membrane of plasmacytoid dendritic cells (pDCs) and in the context of human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection. As the study matured I focused in the study of BDCA-2, a clearly defined regulatory receptor for pDCs, and TIM-3, an emergent putative regulatory receptor of plasmacytoid dendritic cell function. Our results showed the involvement of the tyrosin kinase SYK not only in BDCA-2 signaling pathway but also in the activatory TLR7/9 pathway. We concluded that SYK has a dual role, being active in both activatory and negative/regulatory signalling pathways involved in pDCs activation. Similarly, we explored the MAPkinases MEK and ERK, whic are known to be involved in the BDCA-2 pathway. We found that subliminal concentrations of MEK/ERK inhibitors promote the immunogenic role of pDCs. Lastly, I focused on the study of the role of TIM-3 expressed on pDCs of HIV-1 infected patients, finding an inverse correlation between the levels of TIM-3 on pDCs surface and the efficiency of antiretroviral therapy on the HIV-1 patients.