TY - JOUR
T1 - TLR-stimulated neutrophils instruct NK cells to trigger dendritic cell maturation and promote adaptive T cell responses
AU - Riise, Rebecca E.
AU - Bernson, Elin
AU - Aurelius, Johan
AU - Martner, Anna
AU - Pesce, Silvia
AU - Della Chiesa, Mariella
AU - Marcenaro, Emanuela
AU - Bylund, Johan
AU - Hellstrand, Kristoffer
AU - Moretta, Lorenzo
AU - Moretta, Alessandro
AU - Thorén, Fredrik B.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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. PMNconditioned 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-γ 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.
AB - 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. PMNconditioned 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-γ 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.
UR - http://www.scopus.com/inward/record.url?scp=84937703975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937703975&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1500709
DO - 10.4049/jimmunol.1500709
M3 - Article
C2 - 26085684
AN - SCOPUS:84937703975
VL - 195
SP - 1121
EP - 1128
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -