PhD Scientific Days 2020

Molecular Sciences I. Lectures

Functional Characterization of NLRP3 Inflammasomes in 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

Functional Characterization of NLRP3 Inflammasomes in Human Plasmacytoid Dendritic Cells

Szerző(k) neve és munkahelye

Dóra Bencze1,2, Tünde Fekete1, Angéla-Berki-Pál1, Kitti Pazmandi1
1 Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen
2 Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen, Debrecen

Szekció

Molecular Sciences I. Lectures

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Plasmacytoid dendritic cells (pDCs) are referred to as the most powerful innate immune cells of antiviral responses due to their selective expression of viral nucleic acid sensing endosomal TLRs and their unique capability to produce high amounts of type I IFNs. Furthermore the cytosolic receptors including RIG-I-like helicases evolved for detecting virus replication are also functional in pDCs. However the activity of inflammasome-forming cytosolic receptors such as NLRP3 or their IL-1β producing capacity that can be involved in the antibacterial defense of the cells has not been explored yet.
Aims: In this study we aimed at characterizing the NLRP3 activity in pDCs which could influence the outcome of pDC-mediated immune responses.
Methods: Human pDCs were stimulated with various cell surface or endosomal TLR ligands, NLRP3 activators or live pathogenic and non-pathogenic bacteria then the expression and activity of NLRP3 pathway components were detected by Q-PCR at the mRNA level, and western blotting or ELISA at the protein level.
Results: We found that pDCs express the essential components of the NLRP3 pathway and produce pro-IL-1β upon challenges with TLR ligands or live bacteria. Interestingly, pDCs are able to release the mature form of IL-1β in response to the potassium ionophore nigericin but not to ATP that might be explained by the poor expression of P2X7 purinergic ATP receptors in pDCs. We also observed that pathogenic bacteria have greater capacity to induce NLRP3 activation in these cells in contrast to the commensal ones. Moreover specific inhibition of NLRP3 abolished IL-1β secretion indicating that IL-1β is produced in an NLRP3-dependent manner in pDCs.
Conclusion: Here we demonstrated for the first time that beside their strong antiviral properties pDCs can form active NLRP3 inflammasomes and can be involved in the IL-1-mediated pro-inflammatory responses as well.
Funding: NKFIH FK 128294, EFOP-3.6.3-VEKOP-16-2017-00009 and GINOP-2.3.2-15-2016-00050 projects, UNKP-19-3, UNKP-19-4 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.

Additional Information

Supervisor: Kitti Pazmandi
E-mail address: pazmandikitti@yahoo.de

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4624

Start

10:35

End

10:50

Authors (legacy)

Dóra Bencze1,2, Tünde Fekete1, Angéla-Berki-Pál1, Kitti Pazmandi1
1 Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen
2 Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen, Debrecen