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Published on: May 18, 2016
Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria
Mitchell N Lefebvre1, Fionna A Surette2, Scott M Anthony3
1Department 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.
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.
Insights
Effector memory CD8 T-cells (Tem) rapidly infiltrate the liver during malaria, clearing pathogens. This early recruitment, crucial for liver-stage malaria protection, relies on specific cell interactions.
Area of Science:
- Immunology
- Infectious Diseases
- Hepatology
Background:
- The role of circulating memory CD8 T-cells in liver-stage malaria remains unclear.
- Understanding T-cell dynamics is critical for developing effective malaria treatments.
Purpose of the Study:
- To investigate the trafficking and function of memory CD8 T-cells during liver-stage malaria.
- To elucidate the mechanisms governing CD8 T-cell recruitment to the infected liver.
Main Methods:
- Analysis of CD8 T-cell infiltration in mouse models of malaria and bacterial infection.
- Transcriptional profiling of infected liver tissues.
- Assessment of T-cell recruitment in the absence of resident memory cells.
Main Results:
- Effector memory CD8 T-cells (Tem) infiltrate the liver within 6 hours of infection, mediating pathogen clearance.
- Tem recruitment is associated with rapid inflammatory gene upregulation in Plasmodium-infected livers.
- Recruitment depends on CD8 T-cell-intrinsic LFA-1 and liver phagocytes, occurring independently of resident memory cell function.
Conclusions:
- Tem play a significant role in protection against liver-stage malaria.
- Rapid Tem liver infiltration provides a generalizable mechanism for controlling liver infections.
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