Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity

Microorganisms

MariaGiovanna Desimio¹  Chiara Agrati²  Margherita Doria²  Sara De Minicis³  Rita Casetti³  Veronica Bordoni³  Germana Grassi³  Eleonora Cimini³  Alessandra Sacchi³  Giuseppe Ippolito⁴  Francesca Colavita⁵  Concetta Castilletti⁵  MariaRosaria Capobianchi⁵ 

[1] National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, via Portuense 292, 00149 Rome, Italy;Division of Immunology and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00165 Rome, Italy;Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, via Portuense 292, 00149 Rome, Italy;Scientific Direction;Virology Laboratory, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, via Portuense 292, 00149 Rome, Italy;

关键词: ZIKV;    innate immunity;    Vδ2 T-cells;    antiviral activity;    NKG2D;    cytotoxicity;    perforin;   

DOI  :  10.3390/microorganisms7090350

来源: DOAJ

【 摘 要 】

An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.

【 授权许可】

Unknown