More than they seem: unveiling diverse roles for γδ T cells in the hepatic immune response to parasitic infection 2244

Abstract Description γδ T cells bridge innate and adaptive immunity to complex pathogens, yet they remain understudied compared to conventional T cells, especially within tissues. In mammals, Plasmodium parasites (the causative agents of malaria) establish a clinically silent infection in the liver, a site that is enriched for γδ T cells, before egressing into the blood to cause symptomatic disease. Vaccines targeting liver-stage parasites can prevent future blood-stage infections, necessitating an in-depth study of anti-Plasmodium hepatic immunity. In humans, γδ T cells correlate with live-attenuated malaria parasite vaccine-engendered protection. Therefore, we utilized a mouse model to examine the role of γδ T cells in the host response to Plasmodium parasite infection of the liver. We show via high-parameter mass cytometry that γδ T cells are induced in the liver, spleen, and liver-draining lymph nodes shortly after infection. These induced γδ T cell populations differ by anatomical site and alterations to these populations persist for up to 100 days post-infection, suggesting both innate and adaptive immune roles for γδ T cells. We observed that γδ T cell-deficient mice are defective in innate immune control of parasites while depletion of γδ T cells during immunization completely abrogates protection in mice vaccinated with live-attenuated parasites. Our data demonstrate the importance of the murine model for identifying mechanisms behind γδ T cell modulation of hepatic immunity. Funding Sources Supported by Seattle Children’s Research Institute seed funding for N. Minkah. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)