A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence

Abstract

Despite evidence that γδ Tcells play an important role during malaria, their precise role remains unclear. During murine malaria induced by Plasmodium chabaudi infection and in human P.falciparum infection, we found that γδ Tcells expanded rapidly after resolution of acute parasitemia, in contrast to αβ Tcells that expanded at the acute stage and then declined. Single-cell sequencing showed that TRAV15N-1 (Vδ6.3) γδ Tcells were clonally expanded in mice and had convergent complementarity-determiningregion 3 sequences. These γδ Tcells expressed specific cytokines, M-CSF, CCL5, CCL3, which are known to act on myeloid cells, indicating that this γδ Tcell subset might have distinct functions. Both γδ Tcells and M-CSF were necessary for preventing parasitemic recurrence. These findings point to an M-CSF-producing γδ Tcell subset that fulfills a specialized protective role in the later stage of malaria infection when αβ Tcells have declined.