Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFNγ: Role of CD18, ICAM-1, and ICAM-3

Claudio Costantini, Federica Calzetti, Omar Perbellini, Alessandra Micheletti, Claudia Scarponi, Silvia Lonardi, Martin Pelletier, Knut Schakel, Giovanni Pizzolo, Fabio Facchetti, William Vermi, Cristina Albanesi, Marco A. Cassatella

Research output: Contribution to journalArticlepeer-review

Abstract

The role of neutrophils as key players in the regulation of innate and adaptive immune responses is increasingly being recognized.We report that human neutrophils establish a network with both natural killer (NK) cells and 6-sulfo LacNAc+ dendritic cells (slanDCs), which ultimately serves to up-regulate NK-derived interferon γ (IFNγ). This network involves direct reciprocal interactions and positive amplification loops mediated by cell-derived cytokines. Accordingly, we show that after lipopolysaccharide + interleukin-2 (IL-2) or IL-15/IL-18 stimulation, neutrophils directly interact with and potentiate the activity of both slanDCs and NK cells. On the one hand, neutrophils augment the release of IL-12p70 by slanDCs via a CD18/ intercellular adhesion molecule-1 (ICAM-1) interaction that stimulates activated NK cells to produce IFNγ. IFNγ further potentiates the interaction between neutrophils and slanDCs and the release of slanDC-derived IL-12p70, thus creating a positive feedback loop. On the other hand, neutrophils directly costimulate NK cells via CD18/ ICAM-3, leading to the production of IFNγ. Colocalization of neutrophils, NK cells, and slanDCs, as well as of IL-12p70 and IFNγ, in inflamed tissues of Crohn disease and psoriasis provides strong evidence for a novel cellular and cytokine cooperation within the innate immune system in which neutrophils act as amplifiers of NK cell/slanDC-mediated responses.

Original languageEnglish
Pages (from-to)1677-1686
Number of pages10
JournalBlood
Volume117
Issue number5
DOIs
Publication statusPublished - Feb 3 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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