A polysaccharide virulence factor of a human fungal pathogen induces neutrophil apoptosis via NK cells.
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.
Université 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;
Pauline
P
Robinet
INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche-S CR7, INSERM U1135, F-75013 Paris, France;
Florence
F
Baychelier
Institut Pasteur, Unité des Aspergillus, 75015 Paris, France;
Thierry
T
Fontaine
Centre D'étude des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris, L'hôpital Necker - Enfants Malades, 75743 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, 75015 Paris, France; and.
Capucine
C
Picard
Université 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; Département d'Immunologie, Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
Patrice
P
Debré
INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche-S CR7, INSERM U1135, F-75013 Paris, France;
Vincent
V
Vieillard
Institut Pasteur, Unité des Aspergillus, 75015 Paris, France;
Jean-Paul
JP
Latgé
Université 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; carole.elbim@upmc.fr.
Carole
C
Elbim
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D062610:Fungal Polysaccharides / Q000276:immunology* / Q000633:toxicity; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology* / Q000494:pharmacology
D062610:Fungal Polysaccharides; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017382:Reactive Oxygen Species; D037521:Virulence Factors