title: Activation of NK cell cytotoxicity by aerosolized CpG-ODN/poly(I:C) against lung melanoma metastases is mediated by alveolar macrophages.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy. Electronic address: michele.sommariva@unimi.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Sommariva
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy. Electronic address: valentino.lenoci@unimi.it.
authors.forename: Valentino
authors.initials: V
authors.lastname: Le Noci
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy. Electronic address: chiara.storti@unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Storti
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy. Electronic address: francesca.bianchi1@unimi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: Molecular Targets Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy. Electronic address: elda.tagliabue@istitutotumori.mi.it.
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy; Molecular Targets Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy. Electronic address: andrea.balsari@unimi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Magiagalli 31, 20133 Milan, Italy. Electronic address: lucia.sfondrini@unimi.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sfondrini
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary*; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C519703:TLR3 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma; D011070:Poly I-C
keywords: Alveolar macrophages; Innate immunity; Lung; NK cells; Toll-like receptors