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

  • Cell Rep. 2021 Nov 2;37(5):109956. doi: 10.1016/j.celrep.2021.109956.
Mitchell N Lefebvre  1 ,  Fionna A Surette  2 ,  Scott M Anthony  3 ,  Rahul Vijay  4 ,  Isaac J Jensen  5 ,  Lecia L Pewe  3 ,  Lisa S Hancox  3 ,  Natalija Van Braeckel-Budimir  3 ,  Stephanie van de Wall  3 ,  Stina L Urban  3 ,  Madison R Mix  1 ,  Samarchith P Kurup  3 ,  Vladimir P Badovinac  6 ,  Noah S Butler  2 ,  John T Harty  7
Affiliations
  • 1. 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.
  • 2. 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.
  • 3. Department of Pathology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA.
  • 4. Department of Microbiology and Immunology, University of Iowa, Carver College of Medicine, Iowa City, IA 52246, USA.
  • 5. 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.
  • 6. 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.
  • 7. 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. Electronic address: [email protected].
PMID: 34731605 DOI: 10.1016/j.celrep.2021.109956
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.

Keywords
CD8 T cells; liver-stage immunity; malaria.
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