AUTHOR=Gay Laetitia , Mezouar Soraya , Cano Carla , Foucher Etienne , Gabriac Mélanie , Fullana Marie , Madakamutil Loui , Mège Jean-Louis , Olive Daniel 

TITLE=BTN3A Targeting Vγ9Vδ2 T Cells Antimicrobial Activity Against Coxiella burnetii-Infected Cells

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.915244

DOI=10.3389/fimmu.2022.915244

ISSN=1664-3224

ABSTRACT=<p>Vγ9Vδ2 T cells have been reported to participate to the immune response against infectious diseases such as the Q fever caused by <italic>Coxiella burnetii</italic> infection. Indeed, the number and proportion of Vγ9Vδ2 T cells are increased during the acute phase of Q fever. Human Vγ9Vδ2 T cell responses are triggered by phosphoantigens (pAgs) produced by pathogens and malignant cells, that are sensed <italic>via</italic> the membrane receptors butyrophilin-3A1 (BTN3A1) and -2A1 (BTN2A1). Here, by using CRISPR-Cas9 inactivation in THP-1 cells, we show that BTN3A and BTN2A are required to Vγ9Vδ2 T cell response to <italic>C. burnetii</italic> infection, though not directly involved in the infection process. Furthermore, <italic>C. burnetii</italic>-infected monocytes display increased BTN3A and BTN2A expression and induce Vγ9Vδ2 T cell activation that can be inhibited by specific antagonist mAb. More importantly, we show that the antimicrobial functions of Vγ9Vδ2 T cells towards <italic>C. burnetii</italic> are enhanced in the presence of an BTN3A activating antibody. This supports the role of Vγ9Vδ2 T cells in the control of <italic>C. burnetii</italic> infection and argues in favor of targeting these cells as an alternative treatment strategy for infectious diseases caused by intracellular bacteria.</p>