Transient deficiency of dendritic cells results in lack of a merozoite surface protein 1-specific CD4 T cell response during peak Plasmodium chabaudi blood-stage infection

Anne-Marit Sponaas, Nikolai Belyaev, Mika Falck-Hansen, Alexandre Potocnik, Jean Langhorne

Research output: Contribution to journalArticlepeer-review

Abstract

Splenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8(-) CD11c(high) dendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens of Plasmodium chabaudi-infected mice. However, when isolated during the period of maximum parasitemia and shortly thereafter, the dendritic cells transiently lose their ability to stimulate T cells, recovering only as the parasitemia is controlled. This loss of a CD4 T cell response is also observed in vivo during this part of the infection. CD4 T cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia proliferate poorly, and very few cells produce IFN-γ and interleukin-2 (IL-2), compared with transgenic T cells injected earlier in the blood-stage infection. CD8(-) dendritic cells at day 10 can process and present peptides on major histocompatibility complex (MHC) class II with an efficiency similar to that of dendritic cells from earlier in infection. The failure of the day 10 dendritic cells to activate MSP1-specific CD4 T cells fully in vitro is associated with reduced expression of CD86 and lower production of IL-12 rather than with induction of inhibitory DC receptors or production of IL-10.

Original languageEnglish
Pages (from-to)4248-4256
Number of pages9
JournalInfection and Immunity
Volume80
Issue number12
Early online date12 Nov 2012
DOIs
Publication statusPublished - 31 Dec 2012

Keywords

  • CD86 antigen
  • gamma interferon
  • interleukin 12
  • major histocompatibility antigen class 2
  • membrane protein
  • animal experiment
  • animal model
  • animal tissue
  • article
  • CD4+ T lymphocyte
  • controlled study
  • dendritic cell
  • female
  • human
  • human cell
  • in vitro study
  • in vivo study
  • merozoite
  • mouse
  • nonhuman
  • parasitemia
  • Plasmodium chabaudi
  • Plasmodium chabaudi infection
  • priority journal
  • transgenic mouse
  • Animals
  • Antigen-Presenting Cells
  • CD4-Positive T-Lymphocytes
  • Dendritic Cells
  • Erythrocytes
  • Lymphocyte Activation
  • Malaria
  • Merozoite Surface Protein 1
  • Mice
  • Mice, Inbred BALB C
  • Parasitemia

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