Host Resistance to Plasmodium-Induced Acute Immune Pathology Is Regulated by Interleukin-10 Receptor Signaling

Carla Claser, J Brian de Souza, Samuel G Thorburn, Georges Emile Grau, Eleanor M Riley, Laurent Rénia, Julius C R Hafalla

Research output: Contribution to journalArticlepeer-review

Abstract

The resolution of malaria infection is dependent on a balance between proinflammatory and regulatory immune responses. While early effector T cell responses are required for limiting parasitemia, these responses need to be switched off by regulatory mechanisms in a timely manner to avoid immune-mediated tissue damage. Interleukin-10 receptor (IL-10R) signaling is considered to be a vital component of regulatory responses, although its role in host resistance to severe immune pathology during acute malaria infections is not fully understood. In this study, we have determined the contribution of IL-10R signaling to the regulation of immune responses duringPlasmodium bergheiANKA-induced experimental cerebral malaria (ECM). We show that antibody-mediated blockade of the IL-10R duringP. bergheiANKA infection in ECM-resistant BALB/c mice leads to amplified T cell activation, higher serum gamma interferon (IFN-γ) concentrations, enhanced intravascular accumulation of both parasitized red blood cells and CD8+T cells to the brain, and an increased incidence of ECM. Importantly, the pathogenic effects of IL-10R blockade duringP. bergheiANKA infection were reversible by depletion of T cells and neutralization of IFN-γ. Our findings underscore the importance of IL-10R signaling in preventing T-cell- and cytokine-mediated pathology during potentially lethal malaria infections.

Original languageEnglish
JournalInfection and Immunity
Volume85
Issue number6
Early online date23 May 2017
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Animals
  • Antibodies, Blocking
  • Antibodies, Neutralizing
  • Brain
  • CD8-Positive T-Lymphocytes
  • Erythrocytes
  • Female
  • Interferon-gamma
  • Liver
  • Lymphocyte Activation
  • Malaria, Cerebral
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Parasitemia
  • Plasmodium berghei
  • Receptors, Interleukin-10
  • Signal Transduction
  • Journal Article
  • Research Support, Non-U.S. Gov't

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