title: 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.
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 interferonγ (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 co-stimulate 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.
authors.affiliation: Department of Pathology and Diagnostics, Division of General Pathology, University of Verona, Strada Le Grazie 8, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Costantini
authors.forename: Federica
authors.initials: F
authors.lastname: Calzetti
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micheletti
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarponi
authors.forename: Silvia
authors.initials: S
authors.lastname: Lonardi
authors.forename: Martin
authors.initials: M
authors.lastname: Pelletier
authors.forename: Knut
authors.initials: K
authors.lastname: Schakel
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D000606:Amino Sugars / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D019409:Interleukin-15 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D019409:Interleukin-15; D020382:Interleukin-18; D007376:Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma