Abstract:
:NK cells are important for the control of vaccinia virus (VV) in vivo. Recent studies have shown that multiple pathways are required for effective activation of NK cells. These include both TLR-dependent and -independent pathways, as well as the NKG2D activating receptor that recognizes host stress-induced NKG2D ligands. However, it remains largely unknown what controls the upregulation of NKG2D ligands in response to VV infection. In this study using C57BL/6 mice, we first showed that IL-18 is critical for NK-cell activation and viral clearance. We then demonstrated that IL-18 signaling on both NK cells and DCs is required for efficient NK-cell activation upon VV infection in vitro. We further showed in vivo that efficient NK-cell activation in response to VV is dependent on DCs and IL-18 signaling in non-NK cells, suggesting an essential role for NK cell-extrinsic IL-18 signaling in NK-cell activation. Mechanistically, IL-18 signaling in DCs promotes expression of Rae-1, an NKG2D ligand. Collectively, our data reveal a previously unrecognized role for NK cell-extrinsic IL-18 signaling in NK-cell activation through upregulation of NKG2D ligands. These observations may provide insights into the design of effective NK-cell-based therapies for viral infections and cancer.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Brandstadter JD,Huang X,Yang Ydoi
10.1002/eji.201344134subject
Has Abstractpub_date
2014-09-01 00:00:00pages
2659-66issue
9eissn
0014-2980issn
1521-4141journal_volume
44pub_type
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830090312
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 临床试验,杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830090404
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250839
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pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830160521
更新日期:1986-05-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199807)28:07<2208::AID-IMM
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pub_type: 杂志文章
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:2003-11-01 00:00:00