A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

被引：57
作者：
Robinet, Pauline [1 ,2 ,3 ]
Baychelier, Florence [2 ,3 ]
Fontaine, Thierry
Picard, Capucine [4 ,5 ,6 ]
Debre, Patrice [1 ,2 ,3 ,7 ]
Vieillard, Vincent [2 ,3 ]
Latge, Jean-Paul
Elbim, Carole [1 ,2 ,3 ]
机构：
[1] Univ Paris 06, Sorbonne Univ, Unite Mixte Rech S CR7, F-75005 Paris, France
[2] Univ Paris 06, INSERM, Unite Mixte Rech S CR7, U1135, F-75013 Paris, France
[3] Inst Pasteur, Unite Aspergillus, F-75015 Paris, France
[4] Hop Necker Enfants Malad, AP HP, Ctr Etud Deficits Immunitaires, F-75743 Paris, France
[5] Paris Descartes Univ, Sorbonne Paris Cite, F-75006 Paris, France
[6] Necker Med Sch, Necker Branch, Lab Human Genet Infect Dis, INSERM U980, F-75015 Paris, France
[7] Hop La Pitie Salpetriere, AP HP, Dept Immunol, F-75013 Paris, France
来源：
JOURNAL OF IMMUNOLOGY | 2014年 / 192卷 / 11期
关键词：
ASPERGILLUS-FUMIGATUS; POLYMORPHONUCLEAR LEUKOCYTES; WHOLE-BLOOD; DIFFERENTIATION PROGRAM; INVASIVE ASPERGILLOSIS; MEDIATED APOPTOSIS; SIGNALING PATHWAYS; NKG2D LIGANDS; CROSS-TALK; GLIOTOXIN;
D O I：
10.4049/jimmunol.1303180
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：5332 / 5342
页数：11
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