PhD Scientific Days 2022

Molecular Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Investigating the NLRP3 Pathway Activity in Virus Exposed Human Plasmacytoid Dendritic Cells

Előadó neve

Dr. Bencze, Dóra

Előadó munkahelye

Department of Immunology, Faculty of Medicine, University of Debrecen

Előadó telefonszáma

304722655

Előadó e-mail címe

bencze.dora@med.unideb.hu

Az előadás címe

Investigating the NLRP3 Pathway Activity in Virus Exposed Human Plasmacytoid Dendritic Cells

Szerző(k) neve és munkahelye

Dóra Bencze 1, 2, Kitti Pázmándi 1
1 Department of Immunology, Faculty of Medicine, University of Debrecen
2 Doctoral School of Molecular Cell and Immune Biology, University of Debrecen

Bemutatás módja

Szóbeli

Szekció

Molecular Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Viral infections are often associated with bacterial superinfections, which is partially the result of inhibitory interactions between the antiviral type I interferon (IFN) and the antibacterial NLRP3-dependent IL-1β pathways. These reciprocal antagonistic effects shape the immune responses against pathogens. Plasmacytoid dendritic cells (pDC), as professional type I IFN-producing cells are one of the most potent participants of antiviral immune responses. However, the NLRP3 pathway that determines the immune response to bacterial infections is still unexplored in these cells.
Aims: Thus, we aimed to investigate the interactions of type I IFN and NLRP3-dependent IL-1β pathways in human pDCs.
Methods: In our experiments, a human pDC cell line and primary pDCs were treated with synthetic activators, pathogenic bacteria (E. coli), RNA (VSV) and DNA (HSV) viruses. The NLRP3 pathway activity was monitored by western blot, ELISA, Q-PCR and flow cytometry. The bacterium-induced IL-1β response of pDCs was also determined in the presence of RNA and DNA viruses as well as in the presence of the cytokine IFN-α.
Results: Compared to viruses pathogenic bacteria were observed to induce NLRP3 activation in pDCs to a much larger extent. Furthermore, bacterium-induced IL-1β production can be inhibited in the presence of RNA and DNA viruses, presumably due to the inhibitory effects of virus-induced type I IFNs on the NLRP3-dependent IL-1β pathway. This is further proven by our finding that the presence of the cytokine IFN-α in the cell culture medium significantly reduced the IL-1β production of pDCs by inducing the expression of various NLRP3 pathway inhibitors such as cholesterol-25-hydroxylase, SOCS1 and COP1.
Conclusion: Our results show that antagonistic effects can be observed between the antiviral type I IFN and the antibacterial IL-1β pathways in human pDCs. Thus, the IL-1β-mediated immune responses of pDCs may prevail in inflammatory conditions in which the type I IFN pathway is not dominant.
Funding: NKFIH FK 128294, GINOP-2.3.2-15-2016-00050 projects, UNKP-21-05-DE-170, ÚNKP-21-3-II-DE-21 New National Excellence Program of the Ministry for Innovation and Technology managed by the National Research, Development and Innovation Office and the János Bolyai Research Scholarship from the Hungarian Academy of Sciences.

University and Doctoral School

Debrecen University Faculty of Medicine, Doctoral School of Molecular Cell and Immunobiology

Supervisor

Kitti Pázmándi

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4624

Start

09:30

End

09:45

Authors (legacy)

Dóra Bencze 1, 2, Kitti Pázmándi 1
1 Department of Immunology, Faculty of Medicine, University of Debrecen
2 Doctoral School of Molecular Cell and Immune Biology, University of Debrecen