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

• Published in: Frontiers in immunology Vol. 13; p. 915244
• Main Authors: Gay, Laetitia, Mezouar, Soraya, Cano, Carla, Foucher, Etienne, Gabriac, Mélanie, Fullana, Marie, Madakamutil, Loui, Mège, Jean-Louis, Olive, Daniel
• Format: Journal Article
• Language: English
• Published: Frontiers 27.06.2022; Frontiers Media S.A
• Subjects: antimicrobial immunity; Bacteriology; butyrophilin; Cardiology and cardiovascular system; Coxiella burnetii; Emerging diseases; Human health and pathology; Immunology; Infectious diseases; Life Sciences; Microbiology and Parasitology; Parasitology; therapeutic approaches; Virology; Vγ9Vδ2 T cells; antimicrobial immunity; Vγ9Vδ2 T cells; Coxiella burnetii; therapeutic approaches; butyrophilin
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.915244

Vγ9Vδ2 T cells have been reported to participate to the immune response against infectious diseases such as the Q fever caused by Coxiella burnetii 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 via 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 C. burnetii infection, though not directly involved in the infection process. Furthermore, C. burnetii -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 C. burnetii are enhanced in the presence of an BTN3A activating antibody. This supports the role of Vγ9Vδ2 T cells in the control of C. burnetii infection and argues in favor of targeting these cells as an alternative treatment strategy for infectious diseases caused by intracellular bacteria.