A polysaccharide virulence factor of a human fungal pathogen induces neutrophil apoptosis via NK cells

Pauline Robinet1, Florence Baychelier2, Thierry Fontaine3

  • 1Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche-S CR7, Sorbonne Université, F-75005 Paris, France; INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche-S CR7, INSERM U1135, F-75013 Paris, France;

Insights

Galactosaminogalactan (GG) from Aspergillus fumigatus triggers a novel pathway leading to polymorphonuclear neutrophil (PMN) apoptosis. This process involves reactive oxygen species, NK cells, and Fas signaling, highlighting immune cell crosstalk.

Area of Science:

  • Immunology
  • Mycology
  • Cell Biology

Background:

  • Aspergillus fumigatus is an opportunistic fungal pathogen.
  • Galactosaminogalactan (GG) is a component shed by A. fumigatus.
  • Polymorphonuclear neutrophils (PMNs) and Natural Killer (NK) cells are crucial immune components.

Purpose of the Study:

  • To elucidate the mechanism of GG-induced PMN apoptosis.
  • To investigate the role of NK cells in GG-mediated immune responses.

Main Methods:

  • Investigated GG's effect on PMN apoptosis.
  • Analyzed the role of reactive oxygen species (ROS) and MHC class I chain-related molecule A (MIC-A).
  • Studied the interaction between PMNs and NK cells, focusing on NKG2D and Fas signaling.

Main Results:

  • GG induces PMN apoptosis through an NK cell-dependent mechanism.
  • Reactive oxygen species (ROS) are critical, increasing MIC-A expression on PMNs.
  • This upregulation facilitates NKG2D-mediated NK cell activation, triggering Fas-dependent PMN apoptosis.

Conclusions:

  • PMN apoptosis induced by GG involves a novel crosstalk between PMNs and NK cells.
  • NK cells may contribute to PMN apoptosis in conditions like neutropenia and autoimmune diseases.

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