The role of neutrophils as key players in the regulation of innate and adaptive immune responses is increasingly being recognized. Here, we report that human neutrophils establish a network with both NK cells and 6-sulfo LacNAc(+) dendritic cells (slanDC), which ultimately serves to upregulate NK-derived IFNγ. This network involves direct reciprocal interactions as well as positive amplification loops mediated by cell-derived cytokines. Accordingly, we show that after LPS plus IL-2- or IL-15/IL-18-stimulation, neutrophils directly interact with and potentiate the activity of both slanDC and NK cells. On the one hand, neutrophils augment the release of IL-12p70 by slanDC via a CD18/ICAM-1 interaction that, in turn, stimulates activated NK cells to produce IFNγ. IFNγ, in turn, further potentiates the interaction between neutrophils and slanDC and the release of slanDC-derived IL-12p70, thus creating a positive feedback loop. On the other hand, neutrophils directly co-stimulate NK cells via CD18/ICAM-3, leading to the production of IFNγ. Co-localization of neutrophils, NK cells and slanDC, as well as of IL-12p70 and IFNγ, in inflamed tissues of Crohn's 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.

Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFN{gamma}: role of CD18, ICAM-1 and ICAM-3

COSTANTINI, Claudio;CALZETTI, Federica;PERBELLINI, Omar;MICHELETTI, Alessandra;PIZZOLO, Giovanni;CASSATELLA, Marco Antonio
2011-01-01

Abstract

The role of neutrophils as key players in the regulation of innate and adaptive immune responses is increasingly being recognized. Here, we report that human neutrophils establish a network with both NK cells and 6-sulfo LacNAc(+) dendritic cells (slanDC), which ultimately serves to upregulate NK-derived IFNγ. This network involves direct reciprocal interactions as well as positive amplification loops mediated by cell-derived cytokines. Accordingly, we show that after LPS plus IL-2- or IL-15/IL-18-stimulation, neutrophils directly interact with and potentiate the activity of both slanDC and NK cells. On the one hand, neutrophils augment the release of IL-12p70 by slanDC via a CD18/ICAM-1 interaction that, in turn, stimulates activated NK cells to produce IFNγ. IFNγ, in turn, further potentiates the interaction between neutrophils and slanDC and the release of slanDC-derived IL-12p70, thus creating a positive feedback loop. On the other hand, neutrophils directly co-stimulate NK cells via CD18/ICAM-3, leading to the production of IFNγ. Co-localization of neutrophils, NK cells and slanDC, as well as of IL-12p70 and IFNγ, in inflamed tissues of Crohn's 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.
2011
Human neutrophils; 6-sulfo LacNAc+ DC; NK-derived IFN{gamma}; role of CD18; ICAM-1; ICAM-3
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/346480
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