Neutrophils promote 6-sulfo LacNAc+ dendritic cell (slanDC) survival

• Published in: Journal of leukocyte biology Vol. 94; no. 4; pp. 705 - 710
• Main Authors: Micheletti, Alessandra, Costantini, Claudio, Calzetti, Federica, Camuesco, Deseada, Costa, Sara, Tamassia, Nicola, Cassatella, Marco A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.10.2013
• Subjects: Amino Sugars - metabolism; CD18 Antigens - metabolism; Cell Survival; Cytoprotection; Dendritic Cells - cytology; Dendritic Cells - metabolism; Humans; IL‐15/IL‐18; Intercellular Adhesion Molecule-1 - metabolism; LPS; Neutrophils - cytology; NK cells; NK cells; LPS; IL-15/IL-18
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.1212638

Novel function of human neutrophils, specifically, their capacity to protect slanDCs from accelerated apoptosis under coculture conditions with, or without, NK cells. There is increasing evidence supporting the notion that neutrophils and other leukocytes establish cooperative actions in regulating innate and adaptive immune responses. In such a context, we have shown recently that human neutrophils amplify NK cell/slanDC‐mediated cytokine production by directly costimulating IFN‐γ production by NK cells, as well as by potentiating IL‐12p70 release by slanDCs via CD18/ICAM‐1 interactions. To gain more insights into the molecular bases of the neutrophil‐mediated cytokine potentiation by NK cells and slanDCs under coculture conditions, we now report that neutrophils efficaciously maintain slanDC survival by contact‐dependent mechanisms. Such a phenomenon occurs in the absence or presence of NK cells, which, in the presence of LPS and IL‐2 or the IL‐15/IL‐18 combination, accelerates slanDC apoptosis significantly. Noteworthy, αICAM‐1‐ and αCD18‐neutralizing antibodies, previously shown to suppress IL‐12p70 production by slanDCs and consequently, IFN‐γ by NK cells under similar experimental conditions, did not minimally alter the neutrophil‐mediated prosurvival effect on slanDCs. Altogether, data not only expand our knowledge on the interactions between human neutrophils and slanDCs but also prove that neutrophil‐mediated promotion of slanDC survival and potentiation of slanDC‐derived IL‐12p70 occur via different mechanisms.