Activation of NK cell cytotoxicity by aerosolized CpG-ODN/poly(I:C) against lung melanoma metastases is mediated by alveolar macrophages.
Controversies remain about NK cells direct responsiveness to Toll-like receptor (TLR) agonists or dependence on macrophages. In a melanoma lung metastasis model, aerosolized TLR9 and TLR3 agonists have been reported to induce antitumor immunity through NK cells activation. In the current study, we demonstrated that in vitro TLR9/TLR3 stimulation induced IFN-γ secretion by NK cells, but an increase in their cytotoxicity was detected only after NK cells co-culture with in vitro TLR9/TLR3 agonists pretreated alveolar macrophages. Alveolar macrophages from melanoma lung metastases-bearing mice, treated with aerosolized TLR agonists, also promoted NK cell cytotoxicity. Activated NK cells from lungs of melanoma metastases-bearing mice that were given aerosolized TLR9/TLR3 agonists were able to polarize naive alveolar macrophages toward a M1-like phenotype. Our results demonstrate that activation of NK cells in the lung after TLR engagement is mediated by alveolar macrophages and that activated NK cells shape macrophage behavior.
['Sommariva|Michele|M|', 'Le Noci|Valentino|V|', 'Storti|Chiara|C|', 'Bianchi|Francesca|F|', 'Tagliabue|Elda|E|', 'Balsari|Andrea|A|', 'Sfondrini|Lucia|L|']
D000818:Animals D018920:Coculture Techniques D003602:Cytotoxicity, Immunologic D004195:Disease Models, Animal D005260:Female D006801:Humans D007371:Interferon-gamma D007694:Killer Cells, Natural D008175:Lung Neoplasms D008213:Lymphocyte Activation D016676:Macrophages, Alveolar D008545:Melanoma D008546:Melanoma, Experimental D051379:Mice D008810:Mice, Inbred C57BL D009838:Oligodeoxyribonucleotides D011070:Poly I-C D051196:Toll-Like Receptor 3 D051217:Toll-Like Receptor 9
NK cells Lung Alveolar macrophages Toll-like receptors Innate immunity