期刊论文详细信息
PLoS Pathogens
Modulation of NKp30- and NKp46-Mediated Natural Killer Cell Responses by Poxviral Hemagglutinin
Richard W. Moyer1  Peter C. Turner1  Günter J. Hämmerling2  Dominik Djandji2  Adelheid Cerwenka3  Hartmut Hengel4  Manuela Fiedler4  Carsten Watzl5  André Cohnen5  Frank Momburg6  Mostafa Jarahian6  Cornelius Gati6 
[1] Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, United States of America;Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany;Innate Immunity Junior Research Group, German Cancer Research Center, Heidelberg, Germany;Institute for Virology, Heinrich-Heine-University, Düsseldorf, Germany;Institute of Immunology, University of Heidelberg, Heidelberg, Germany;Translational Immunology Research Unit, German Cancer Research Center, Heidelberg, Germany
关键词: NK cells;    HeLa cells;    Cell staining;    Cell binding;    Enzyme-linked immunoassays;    Antibodies;    Lysis (medicine);    Recombinant proteins;   
DOI  :  10.1371/journal.ppat.1002195
学科分类:生物科学(综合)
来源: Public Library of Science
PDF
【 摘 要 】

Natural killer (NK) cells are an important element in the immune defense against the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK cells are regulated through inhibitory and activating signaling receptors, the latter involving NKG2D and the natural cytotoxicity receptors (NCR), NKp46, NKp44 and NKp30. Here we report that VV infection results in an upregulation of ligand structures for NKp30 and NKp46 on infected cells, whereas the binding of NKp44 and NKG2D was not significantly affected. Likewise, infection with ectromelia virus (ECTV), the mousepox agent, enhanced binding of NKp30 and, to a lesser extent, NKp46. The hemagglutinin (HA) molecules from VV and ECTV, which are known virulence factors, were identified as novel ligands for NKp30 and NKp46. Using NK cells with selectively silenced NCR expression and NCR-CD3ζ reporter cells, we observed that HA present on the surface of VV-infected cells, or in the form of recombinant soluble protein, was able to block NKp30-triggered activation, whereas it stimulated the activation through NKp46. The net effect of this complex influence on NK cell activity resulted in a decreased NK lysis susceptibility of infected cells at late time points of VV infection when HA was expression was pronounced. We conclude that poxviral HA represents a conserved ligand of NCR, exerting a novel immune escape mechanism through its blocking effect on NKp30-mediated activation at a late stage of infection.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO201902015927214ZK.pdf 2345KB PDF download
  文献评价指标  
  下载次数:16次 浏览次数:8次