Format

Send to

Choose Destination
J Immunol. 2015 Aug 1;195(3):1121-8. doi: 10.4049/jimmunol.1500709. Epub 2015 Jun 17.

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

Author information

1
Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
2
Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy;
3
Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy; Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, 16132 Genoa, Italy;
4
Department of Oral Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden; and.
5
Istituto Giannina Gaslini, 16147 Genoa, Italy.
6
Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden; fredrik.thoren@gu.se.

Abstract

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-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.

PMID:
26085684
DOI:
10.4049/jimmunol.1500709
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center