Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria

SUMMARY

Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector memory CD8 T cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections and mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires CD8 T cell-intrinsic LFA-1 expression and the presence of liver phagocytes. Rapid Tem liver infiltration is distinct from recruitment to other non-lymphoid tissues in that it occurs both in the absence of liver tissue resident memory “sensing-and-alarm” function and ~42 hours earlier than in lung infection by influenza virus. These data demonstrate relevance for Tem in protection against malaria and provide generalizable mechanistic insights germane to control of liver infections.

In brief

Lefebvre et al. describe the dynamics and mechanisms by which circulating memory CD8 T cells infiltrate the liver to control local malaria and bacterial infection. This work suggests that circulating memory CD8 T cells could be useful targets for developing vaccines and therapeutics for malaria and other liver-specific pathogens.

Graphical abstract