IL-15 cis Presentation Is Required for Optimal NK Cell Activation in Lipopolysaccharide-Mediated Inflammatory Conditions

Ivan Zanoni, Roberto Spreafico, Caterina Bodio, Marco DiGioia, Clara Cigni, Achille Broggi, Tatiana Gorletta, Michele Caccia, Giuseppe Chirico, Laura Sironi, Maddalena Collini, Mario P. Colombo, Natalio Garbi, Francesca Granucci

Research output: Contribution to journalArticlepeer-review

Abstract

Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E.coli exposure, dendritic cells (DCs) produce three cytokines-interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)-necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis-presented NK cell-derived and trans-presentedDC-derived IL-15 contribute equally to optimal NK cell activation

Original languageEnglish
Pages (from-to)1235-1249
Number of pages15
JournalCell Reports
Volume4
Issue number6
DOIs
Publication statusPublished - Sep 26 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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