Human plasmacytoid dendritic cells at the crossroad of type I interferon-regulated B cell differentiation and antiviral response to tick-borne encephalitis virus

• DOI: 10.1371/journal.ppat.1009505
• Publication Date: 2021-04-16T09:23:57Z
• Authors: Marilena P. Etna; Aurora Signorazzi; Daniela Ricci; Martina Severa; Fabiana Rizzo; Elena Giacomini; Andrea Gaggioli; Isabelle Bekeredj...; Anke Huckriede; Eliana M. Coccia
• Keywords: 0301 basic medicine; Host Microbial Interactions; Cell differentiation ; Glycoproteins ; Frühjahr-Sommer-Encephalitis ; Immune response ; Hydroxides ; Vaccines ; Aluminum ; B cells ; Viral vaccines; QH301-705.5; Cell Differentiation; Viral Vaccines; Dendritic Cells; RC581-607; Lymphocyte Activation; Antiviral Agents; Encephalitis Viruses, Tick-Borne; 3. Good health; 03 medical and health sciences; Viral Envelope Proteins; Interferon Type I; Leukocytes, Mononuclear; Cytokines; Humans; RNA, Viral; Immunologic diseases. Allergy; Biology (General); Chemokines; Encephalitis, Tick-Borne; Research Article

The Tick-borne encephalitis virus (TBEV) causes different disease symptoms varying from asymptomatic infection to severe and meningitis suggesting a crucial role of the human host immune system in determining fate infection. There is need understand mechanisms underpinning TBEV-host interactions leading protective immunity. To this aim, we studied response peripheral blood mononuclear cells (PBMC) whole formaldehyde inactivated TBEV (I-TBEV), drug substance Encepur, one five commercially available vaccine. Immunophenotyping, transcriptome cytokine profiling PBMC revealed that I-TBEV generates differentiation sub-population plasmacytoid dendritic (pDC) specialized type I interferon (IFN) production. In contrast, likely due presence aluminum hydroxide, Encepur vaccine was poor pDC stimulus. We demonstrated I-TBEV-induced IFN together with Interleukin 6 BAFF be critical for B cell plasmablasts as measured by immunophenotyping immunoglobulin Robust secretion induced concerted action both viral E glycoprotein RNA mirroring previous data on dual stimulation S . aureus influenza protein nucleic acid leads IFN-mediated sustained response. neutralization or high temperature denaturation inhibition Toll-like receptor 7 signalling confirmed importance preserving functional integrity these key molecules during inactivation procedure manufacturing process produce able stimulate strong responses.