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

J Immunol. 2014 Jun 1;192(11):5332-42. doi: 10.4049/jimmunol.1303180. Epub 2014 Apr 30.


Aspergillus fumigatus is an opportunistic human fungal pathogen that sheds galactosaminogalactan (GG) into the environment. Polymorphonuclear neutrophils (PMNs) and NK cells are both part of the first line of defense against pathogens. We recently reported that GG induces PMN apoptosis. In this study, we show that PMN apoptosis occurs via a new NK cell-dependent mechanism. Reactive oxygen species, induced by the presence of GG, play an indispensable role in this apoptotic effect by increasing MHC class I chain-related molecule A expression at the PMN surface. This increased expression enables interaction between MHC class I chain-related molecule A and NKG2D, leading to NK cell activation, which in turn generates a Fas-dependent apoptosis-promoting signal in PMNs. Taken together, our results demonstrate that the crosstalk between PMNs and NK cells is essential to GG-induced PMN apoptosis. NK cells might thus play a role in the induction of PMN apoptosis in situations such as unexplained neutropenia or autoimmune diseases.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Aspergillus fumigatus / immunology*
  • Aspergillus fumigatus / pathogenicity
  • Female
  • Fungal Polysaccharides / immunology*
  • Fungal Polysaccharides / toxicity
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Male
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Reactive Oxygen Species / immunology
  • Virulence Factors / immunology*
  • Virulence Factors / pharmacology


  • Fungal Polysaccharides
  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • MHC class I-related chain A
  • NK Cell Lectin-Like Receptor Subfamily K
  • Reactive Oxygen Species
  • Virulence Factors