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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses

Journal article
Authors Rebecca E Riise
Elin Bernson
Johan Aurelius
Anna Martner
S. Pesce
M. Della Chiesa
E. Marcenaro
Johan Bylund
Kristoffer Hellstrand
L. Moretta
A. Moretta
Fredrik Bergh Thorén
Published in Journal of Immunology
Volume 195
Issue 3
Pages 1121-1128
ISSN 0022-1767
Publication year 2015
Published at Institute of Odontology
Sahlgrenska Cancer Center
Pages 1121-1128
Language en
Subject categories Immunology in the medical area


Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-gamma production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.

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