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

Pauline Robinet (1, 2) , Florence Baychelier (2) , Thierry Fontaine (3) , Capucine Picard (4, 5, 6) , Patrice Debré (1, 2, 7) , Vincent Vieillard (2) , Jean-Paul Latge (3) , Carole Elbim (1, 2)

1 UPMC - Université Pierre et Marie Curie - Paris 6
2 CIMI - Centre d'Immunologie et de Maladies Infectieuses
3 Aspergillus
4 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
5 UPD5 - Université Paris Descartes - Paris 5
6 Inserm U980 - Génétique Humaine des Maladies Infectieuses
7 CHU Pitié-Salpêtrière [AP-HP]

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.

Domaines: Sciences du Vivant [q-bio]; Mycologie

Pauline Robinet, Florence Baychelier, Thierry Fontaine, Capucine Picard, Patrice Debré, et al.. A polysaccharide virulence factor of a human fungal pathogen induces neutrophil apoptosis via NK cells.. Journal of Immunology, 2014, 192 (11), pp.5332 - 5342. ⟨10.4049/jimmunol.1303180⟩. ⟨pasteur-01724671⟩