Transcriptional Memory-Like Imprints and Enhanced Functional Activity in γδ T Cells Following Resolution of Malaria Infection

Abstract

γδ T cells play an essential role in the immune response to many pathogens, including <i>Plasmodium</i>. However, long-lasting effects of infection on the γδ T cell population still remain inadequately understood. This study focused on assessing molecular and functional changes that persist in the γδ T cell population following resolution of malaria infection. We investigated transcriptional changes and memory-like functional capacity of malaria pre-exposed γδ T cells using a <i>Plasmodium</i><i>chabaudi</i> infection model. We show that multiple genes associated with effector function (chemokines, cytokines and cytotoxicity) and antigen-presentation were upregulated in <i>P. chabaudi</i>-exposed γδ T cells compared to γδ T cells from naïve mice. This transcriptional profile was positively correlated with profiles observed in conventional memory CD8⁺ T cells and was accompanied by enhanced reactivation upon secondary encounter with <i>Plasmodium</i>-infected red blood cells <i>in vitro</i>. Collectively our data demonstrate that <i>Plasmodium</i> exposure result in "memory-like imprints" in the γδ T cell population and also promotes γδ T cells that can support antigen-presentation during subsequent infections.