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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
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;
Abstract:
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.
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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