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Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum

Myriam Baratin1, Sophie Roetynck, Catherine Lépolard

  • 1Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université delaMéditerranée, 13288 Marseille, France.

Proceedings of the National Academy of Sciences of the United States of America
|October 6, 2005
PubMed

Insights

Macrophages are essential for natural killer (NK) cell interferon-gamma (IFN-gamma) secretion against malaria. This study reveals a novel pathway involving IL-18 and MyD88 for parasite-specific NK cell activation.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Cell Biology

Background:

  • Natural killer (NK) cells are crucial for anti-tumor and anti-viral immunity, often requiring cooperation with dendritic cells.
  • NK cell activation pathways are complex and vary depending on the stimulus and cellular context.

Purpose of the Study:

  • To elucidate the mechanism of NK cell activation in response to Plasmodium falciparum (Pf) infected erythrocytes.
  • To identify the cellular and molecular players involved in this specific immune response.

Main Methods:

  • Investigated NK cell IFN-gamma secretion in response to Pf-infected erythrocytes.
  • Assessed the role of macrophages, Toll-like receptors (TLRs), IL-18 receptor (IL-18R), and MyD88 in NK cell activation.
  • Analyzed chemokine production (CXCL8) and cytolytic activity of NK cells.

Main Results:

  • Macrophages are mandatory for NK cell IFN-gamma secretion against Pf-infected erythrocytes.
  • Direct sensing of Pf infection by NK cells induces CXCL8 production but not cytolysis.
  • TLR2, TLR9, and TLR11 are not individually required for this NK cell activation.
  • IL-18R on NK cells, IL-18 from macrophages, and MyD88 on both cell types are essential for this pathway.

Conclusions:

  • A novel pathway for NK cell activation by Plasmodium falciparum involves macrophage-derived IL-18 and MyD88 signaling.
  • This pathway is critical for IFN-gamma production by NK cells during malaria infection.
  • NK cells can be activated to produce cytokines without engaging their cytolytic functions.

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