Transcriptomic profile of TNFhigh MAIT cells is linked to B cell response following SARS-CoV-2 vaccination

Frontiers in Immunology

Immunology

Antonio Voza¹  Simone Balin²  Paolo Marzano²  Alessandro Frigo³  Valentina Cazzetta³  Francesca Calcaterra³  Michela Calvi³  Domenico Mavilio³  Ahmed Darwish³  Silvia Della Bella³  Sara Franzese³  Assunta Cancellara³  Rocco Piazza⁴  Sarina Ravens⁵  Inga Sandrock⁵  Immo Prinz⁶  Likai Tan⁷  Clara Di Vito⁸  Anna Carletti⁸  Joanna Mikulak⁸  Sara Terzoli⁹ 

[1]Department of Biomedical Sciences, Humanitas University, Milan, Italy

[2]Department of Biomedical Unit, IRCCS Humanitas Research Hospital, Milan, Italy

[3]Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

[4]Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

[5]Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy

[6]Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy

[7]Institute of Immunology, Hannover Medical School (MHH), Hannover, Germany

[8]Institute of Immunology, Hannover Medical School (MHH), Hannover, Germany

[9]Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[10]Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[11]Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy

[12]Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Milan, Italy

[13]Department of Biomedical Sciences, Humanitas University, Milan, Italy

关键词: SARS-CoV-2;    mRNA vaccine;    MAIT cells;    immune response;    TNF;    B cells;    single-cell RNA/TCR-sequencing;   

DOI  :  10.3389/fimmu.2023.1208662

 received in 2023-04-19, accepted in 2023-06-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionHigher frequencies of mucosal-associated invariant T (MAIT) cells were associated with an increased adaptive response to mRNA BNT162b2 SARS-CoV-2 vaccine, however, the mechanistic insights into this relationship are unknown. In the present study, we hypothesized that the TNF response of MAIT cells supports B cell activation following SARS-CoV-2 immunization.MethodsTo investigate the effects of repeated SARS-CoV-2 vaccinations on the peripheral blood mononuclear cells (PBMCs), we performed a longitudinal single cell (sc)RNA-seq and scTCR-seq analysis of SARS-CoV-2 vaccinated healthy adults with two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Collection of PBMCs was performed 1 day before, 3 and 17 days after prime vaccination, and 3 days and 3 months following vaccine boost. Based on scRNA/TCR-seq data related to regulatory signals induced by the vaccine, we used computational approaches for the functional pathway enrichment analysis (Reactome), dynamics of the effector cell-polarization (RNA Velocity and CellRank), and cell-cell communication (NicheNet).ResultsWe identified MAIT cells as an important source of TNF across circulating lymphocytes in response to repeated SARS-CoV-2 BNT162b2 vaccination. The TNFhigh signature of MAIT cells was induced by the second administration of the vaccine. Notably, the increased TNF expression was associated with MAIT cell proliferation and efficient anti-SARS-CoV-2 antibody production. Finally, by decoding the ligand-receptor interactions and incorporating intracellular signaling, we predicted TNFhigh MAIT cell interplay with different B cell subsets. In specific, predicted TNF-mediated activation was selectively directed to conventional switched memory B cells, which are deputed to high-affinity long-term memory.DiscussionOverall, our results indicate that SARS-CoV-2 BNT162b2 vaccination influences MAIT cell frequencies and their transcriptional effector profile with the potential to promote B cell activation. This research also provides a blueprint for the promising use of MAIT cells as cellular adjuvants in mRNA-based vaccines.

【 授权许可】

Unknown   
Copyright © 2023 Marzano, Balin, Terzoli, Della Bella, Cazzetta, Piazza, Sandrock, Ravens, Tan, Prinz, Calcaterra, Di Vito, Cancellara, Calvi, Carletti, Franzese, Frigo, Darwish, Voza, Mikulak and Mavilio