{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:33:15Z","timestamp":1791214395953,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The mechanisms for NK cell activation during infection by intracellular bacterial pathogens are not clearly defined. To dissect how Listeria monocytogenes infection elicits NK cell activation, we evaluated the requirements for activation of naive splenic NK cells by infected bone marrow-derived dendritic cells (BMDCs). We found that NK cell activation in this setting required infection of BMDCs by live wild type bacteria. NK cells were not activated when BMDCs were infected with a live hemolysin deficient (\u0394hly) strain. Neutralization of IL-12, TNF-\u03b1, or caspase-1 each dramatically reduced NK cell IFN-\u03b3 production in response to live wt L. monocytogenes infection. Addition of recombinant IL-18, but not IL-1\u03b2, reversed the effects of caspase-1 inhibition. Recombinant IL-18 also restored NK cell activation by BMDCs infected with \u0394hly L. monocytogenes, which produced IL-12 but not IL-18. IL-18 acted on NK cells because MyD88 expression was required in responding NK cells, but not infected BMDC. However, secreted cytokines were not sufficient for activation of naive NK cells by infected BMDCs. Rather, NK cell activation additionally required contact between infected BMDCs and NK cells. These data suggest that the activation of NK cells during L. monocytogenes infection requires both secreted cytokines and ligation of NK activating receptors during direct contact with infected DCs.<\/jats:p>","DOI":"10.4049\/jimmunol.0903759","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T23:34:10Z","timestamp":1269905650000},"page":"5172-5178","source":"Crossref","is-referenced-by-count":54,"title":["Activation of Naive NK Cells in Response to\n                    <i>Listeria monocytogenes<\/i>\n                    Requires IL-18 and Contact with Infected Dendritic Cells"],"prefix":"10.1093","volume":"184","author":[{"given":"Jessica","family":"Humann","sequence":"first","affiliation":[{"name":"National Jewish Health and Integrated Department of Immunology, University of Colorado , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel L","family":"Lenz","sequence":"additional","affiliation":[{"name":"National Jewish Health and Integrated Department of Immunology, University of Colorado , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,1]]},"reference":[{"key":"2026012808083283500_r1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ni1581","article-title":"Up on the tightrope: natural killer cell activation and inhibition.","volume":"9","author":"Lanier","year":"2008","journal-title":"Nat. Immunol."},{"key":"2026012808083283500_r2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells.","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat. Immunol."},{"key":"2026012808083283500_r3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/eji.200636910","article-title":"New vistas on macrophage differentiation and activation.","volume":"37","author":"Mantovani","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2026012808083283500_r4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev.immunol.17.1.189","article-title":"Natural killer cells in antiviral defense: function and regulation by innate cytokines.","volume":"17","author":"Biron","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"2026012808083283500_r5","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2007.03.006","article-title":"Dendritic cells prime natural killer cells by trans-presenting interleukin 15.","volume":"26","author":"Lucas","year":"2007","journal-title":"Immunity"},{"key":"2026012808083283500_r6","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S1359-6101(03)00043-1","article-title":"The biology of IL-12: coordinating innate and adaptive immune responses.","volume":"14","author":"Watford","year":"2003","journal-title":"Cytokine Growth Factor Rev."},{"key":"2026012808083283500_r7","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S1286-4579(02)00036-9","article-title":"Regulatory pathways involved in the infection-induced production of IFN-gamma by NK cells.","volume":"4","author":"Lieberman","year":"2002","journal-title":"Microbes Infect."},{"key":"2026012808083283500_r8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/intimm\/dxl148","article-title":"Type 1 cytokine\/chemokine production by mouse NK cells following activation of their TLR\/MyD88-mediated pathways.","volume":"19","author":"Sawaki","year":"2007","journal-title":"Int. Immunol."},{"key":"2026012808083283500_r9","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.4049\/jimmunol.181.3.1627","article-title":"Cutting edge: Priming of NK cells by IL-18.","volume":"181","author":"Chaix","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808083283500_r10","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.4049\/jimmunol.169.7.3863","article-title":"Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice.","volume":"169","author":"Seki","year":"2002","journal-title":"J. Immunol."},{"key":"2026012808083283500_r11","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1128\/IAI.70.5.2657-2664.2002","article-title":"Listeria monocytogenes infection in caspase-11-deficient mice.","volume":"70","author":"Mueller","year":"2002","journal-title":"Infect. Immun."},{"key":"2026012808083283500_r12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/intimm\/dxh041","article-title":"Roles of caspase-1 in Listeria infection in mice.","volume":"16","author":"Tsuji","year":"2004","journal-title":"Int. Immunol."},{"key":"2026012808083283500_r13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/sj.cdd.4402026","article-title":"The inflammatory caspases: guardians against infections and sepsis.","volume":"14","author":"Scott","year":"2007","journal-title":"Cell Death Differ."},{"key":"2026012808083283500_r14","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrmicro1413","article-title":"Listeria monocytogenes: a multifaceted model.","volume":"4","author":"Hamon","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"2026012808083283500_r15","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.1128\/IAI.01779-06","article-title":"Cytolysin-dependent escape of the bacterium from the phagosome is required but not sufficient for induction of the Th1 immune response against Listeria monocytogenes infection: distinct role of Listeriolysin O determined by cytolysin gene replacement.","volume":"75","author":"Hara","year":"2007","journal-title":"Infect. Immun."},{"key":"2026012808083283500_r16","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.4049\/jimmunol.158.11.5297","article-title":"Impaired macrophage listericidal and cytokine activities are responsible for the rapid death of Listeria monocytogenes-infected IFN-gamma receptor-deficient mice.","volume":"158","author":"Dai","year":"1997","journal-title":"J. Immunol."},{"key":"2026012808083283500_r17","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1126\/science.8456301","article-title":"Immune response in mice that lack the interferon-gamma receptor.","volume":"259","author":"Huang","year":"1993","journal-title":"Science"},{"key":"2026012808083283500_r18","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nri1461","article-title":"Immune responses to Listeria monocytogenes.","volume":"4","author":"Pamer","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808083283500_r19","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.imbio.2005.07.003","article-title":"Sources of interferon-gamma (IFN-gamma) in early immune response to Listeria monocytogenes.","volume":"210","author":"Th\u00e4le","year":"2005","journal-title":"Immunobiology"},{"key":"2026012808083283500_r20","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.4049\/jimmunol.178.4.2407","article-title":"Expression of the p60 autolysin enhances NK cell activation and is required for listeria monocytogenes expansion in IFN-gamma-responsive mice.","volume":"178","author":"Humann","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808083283500_r21","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.4049\/jimmunol.152.4.1873","article-title":"Role of NK1.1+ cells in experimental listeriosis. NK1+ cells are early IFN-gamma producers but impair resistance to Listeria monocytogenes infection.","volume":"152","author":"Teixeira","year":"1994","journal-title":"J. Immunol."},{"key":"2026012808083283500_r22","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.4049\/jimmunol.0803329","article-title":"Interactions between human NK cells and macrophages in response to Salmonella infection.","volume":"182","author":"Lapaque","year":"2009","journal-title":"J. Immunol."},{"key":"2026012808083283500_r23","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.4049\/jimmunol.162.10.5894","article-title":"IL-18 and CD28 use distinct molecular mechanisms to enhance NK cell production of IL-12-induced IFN-gamma.","volume":"162","author":"Walker","year":"1999","journal-title":"J. Immunol."},{"key":"2026012808083283500_r24","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0928-8244(02)00470-4","article-title":"Production of IL-12 and IL-18 in human dendritic cells upon infection by Listeria monocytogenes.","volume":"35","author":"Kolb-M\u00e4urer","year":"2003","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"2026012808083283500_r25","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.4049\/jimmunol.173.6.3594","article-title":"Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cells.","volume":"173","author":"Koka","year":"2004","journal-title":"J. Immunol."},{"key":"2026012808083283500_r26","doi-asserted-by":"crossref","first-page":"7859","DOI":"10.4049\/jimmunol.180.12.7859","article-title":"Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm.","volume":"180","author":"Hara","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808083283500_r27","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1074-7613(00)80543-9","article-title":"Defective NK cell activity and Th1 response in IL-18-deficient mice.","volume":"8","author":"Takeda","year":"1998","journal-title":"Immunity"},{"key":"2026012808083283500_r28","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1128\/IAI.70.3.1049-1055.2002","article-title":"Essential role of interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells.","volume":"70","author":"Nomura","year":"2002","journal-title":"Infect. Immun."},{"key":"2026012808083283500_r29","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1128\/IAI.00994-08","article-title":"Dendritic cell and NK cell reciprocal cross talk promotes gamma interferon-dependent immunity to blood-stage Plasmodium chabaudi AS infection in mice.","volume":"77","author":"Ing","year":"2009","journal-title":"Infect. Immun."},{"key":"2026012808083283500_r30","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.immuni.2008.09.017","article-title":"Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells.","volume":"29","author":"Kang","year":"2008","journal-title":"Immunity"},{"key":"2026012808083283500_r31","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1182\/blood-2004-01-0380","article-title":"NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs.","volume":"104","author":"Borg","year":"2004","journal-title":"Blood"},{"key":"2026012808083283500_r32","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1182\/blood-2004-10-3906","article-title":"NK\/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.","volume":"106","author":"Semino","year":"2005","journal-title":"Blood"},{"key":"2026012808083283500_r33","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.4049\/jimmunol.178.5.2688","article-title":"NKp46 and NKG2D recognition of infected dendritic cells is necessary for NK cell activation in the human response to influenza infection.","volume":"178","author":"Draghi","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808083283500_r34","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.4049\/jimmunol.179.6.3472","article-title":"Engagement of TLR3, TLR7, and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12.","volume":"179","author":"Girart","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808083283500_r35","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/ni1524","article-title":"NKG2D signaling is coupled to the interleukin 15 receptor signaling pathway.","volume":"8","author":"Horng","year":"2007","journal-title":"Nat. Immunol."},{"key":"2026012808083283500_r36","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nri1199","article-title":"Roles of the NKG2D immunoreceptor and its ligands.","volume":"3","author":"Raulet","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808083283500_r37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.4049\/jimmunol.175.2.720","article-title":"Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo.","volume":"175","author":"Wiemann","year":"2005","journal-title":"J. Immunol."},{"key":"2026012808083283500_r38","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-2567.2005.02259.x","article-title":"NK cell activity in tuberculosis is associated with impaired CD11a and ICAM-1 expression: a regulatory role of monocytes in NK activation.","volume":"116","author":"Schierloh","year":"2005","journal-title":"Immunology"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/9\/5172\/62718968\/ji_0903759.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/9\/5172\/62718968\/ji_0903759.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:09:13Z","timestamp":1769605753000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/9\/5172\/8013409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,1]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,5,1]]},"published-print":{"date-parts":[[2010,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0903759","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,5]]},"published":{"date-parts":[[2010,5,1]]}}}