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

快速将循环记忆性 CD8 T 细胞募集到肝脏有助于控制疟疾

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作者:Mitchell N Lefebvre,Fionna A Surette,Scott M Anthony,Rahul Vijay,Isaac J Jensen,Lecia L Pewe,Lisa S Hancox,Natalija Van Braeckel-Budimir,Stephanie van de Wall,Stina L Urban,Madison R Mix,Samarchith P Kurup,Vladimir P Badovinac,Noah S Butler,John T Harty

Abstract

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.

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