Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria
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
Affiliations
Mitchell N. Lefebvre
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Medical Scientist Training Program, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA
Fionna A. Surette
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA; Department of Microbiology and Immunology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Scott M. Anthony
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Rahul Vijay
Department of Microbiology and Immunology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Isaac J. Jensen
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA
Lecia L. Pewe
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Lisa S. Hancox
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Natalija Van Braeckel-Budimir
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Stephanie van de Wall
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Stina L. Urban
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Madison R. Mix
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Medical Scientist Training Program, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA
Samarchith P. Kurup
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Vladimir P. Badovinac
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA; Department of Microbiology and Immunology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
Noah S. Butler
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA; Department of Microbiology and Immunology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA
John T. Harty
Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52246, USA; Corresponding author
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.
