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

Riise, Rebecca E,1987Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg (författare)

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.

Bernson, Elin,1987Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg(Swepub:cth)bernson (författare)
Aurelius, Johan,1980Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg(Swepub:gu)xaurjo (författare)
Martner, Anna,1979Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg(Swepub:gu)xbigan (författare)
Pesce, S. (författare)
Della Chiesa, M. (författare)
Marcenaro, E. (författare)
Bylund, Johan,1975Gothenburg University,Göteborgs universitet,Institutionen för odontologi,Institute of Odontology,University of Gothenburg(Swepub:gu)xbyljo (författare)
Hellstrand, Kristoffer,1956Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg(Swepub:gu)xhellk (författare)
Moretta, L. (författare)
Moretta, A. (författare)
Bergh Thorén, Fredrik,1976Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,University of Gothenburg(Swepub:gu)xthofr (författare)
Göteborgs universitetSahlgrenska Cancer Center (creator_code:org_t)

Ingår i:Journal of Immunology: The American Association of Immunologists195:3, s. 1121-11280022-17671550-6606

Av författaren/redakt...: Riise, Rebecca E ...; Bernson, Elin, 1 ...; Aurelius, Johan, ...; Martner, Anna, 1 ...; Pesce, S.; Della Chiesa, M.; visa fler...; Marcenaro, E.; Bylund, Johan, 1 ...; Hellstrand, Kris ...; Moretta, L.; Moretta, A.; Bergh Thorén, Fr ...; visa färre...

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