{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:56:01Z","timestamp":1793652961453,"version":"4.5.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["342168; 184228"],"award-info":[{"award-number":["342168; 184228"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytokine responses from monocytes and macrophages exposed to bacteria are of particular importance in innate immunity. Focusing on the impact of the immunoregulatory cytokine interleukin (IL)-27 on control of innate immune system responses, we examined human immune responses to bacterial products and bacterial infection by <jats:italic>E. coli<\/jats:italic> and <jats:italic>S. typhimurium<\/jats:italic>. Since the effect of IL-27 treatment in human myeloid cells infected with bacteria is understudied, we treated human monocytes and macrophages with IL-27 and either LPS, flagellin, or bacteria, to investigate the effect on inflammatory signaling and cytokine responses. We determined that simultaneous stimulation with IL-27 and LPS derived from <jats:italic>E. coli<\/jats:italic> or <jats:italic>S. typhimurium<\/jats:italic> resulted in enhanced IL-12p40, TNF-\u03b1, and IL-6 expression compared to that by LPS alone. To elucidate if IL-27 manipulated the cellular response to infection with bacteria, we infected IL-27 treated human macrophages with <jats:italic>S. typhimurium<\/jats:italic>. While IL-27 did not affect susceptibility to <jats:italic>S. typhimurium<\/jats:italic> infection or <jats:italic>S. typhimurium<\/jats:italic>-induced cell death, IL-27 significantly enhanced proinflammatory cytokine production in infected cells. Taken together, we highlight a role for IL-27 in modulating innate immune responses to bacterial infection.<\/jats:p>","DOI":"10.1038\/s41598-018-32007-y","type":"journal-article","created":{"date-parts":[[2018,9,6]],"date-time":"2018-09-06T11:32:58Z","timestamp":1536233578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["IL-27 amplifies cytokine responses to Gram-negative bacterial products and Salmonella typhimurium infection"],"prefix":"10.1038","volume":"8","author":[{"given":"C.","family":"Petes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Odoardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Plater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. L.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Gee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,12]]},"reference":[{"key":"32007_CR1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/S1074-7613(03)00296-6","volume":"19","author":"G Trinchieri","year":"2003","unstructured":"Trinchieri, G., Pflanz, S. & Kastelein, R. A. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 19, 641\u2013644 (2003).","journal-title":"Immunity"},{"key":"32007_CR2","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/S1074-7613(02)00324-2","volume":"16","author":"S Pflanz","year":"2002","unstructured":"Pflanz, S. et al. IL-27, a Heterodimeric Cytokine Composed of EBI3 and p28 Protein, Induces Proliferation of Naive CD4+ T Cells. Immunity 16, 779\u2013790 (2002).","journal-title":"Immunity"},{"key":"32007_CR3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/ar1227","volume":"6","author":"AV Villarino","year":"2004","unstructured":"Villarino, A. V. & Hunter, C. A. Biology of recently discovered cytokines: discerning the pro-and anti-inflammatory properties of interleukin-27. Arthritis Research And Therapy 6, 225\u2013225 (2004).","journal-title":"Arthritis Research And Therapy"},{"key":"32007_CR4","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.4049\/jimmunol.172.4.2225","volume":"172","author":"S Pflanz","year":"2004","unstructured":"Pflanz, S. et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. The Journal of Immunology 172, 2225\u20132231 (2004).","journal-title":"The Journal of Immunology"},{"key":"32007_CR5","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1146\/annurev.immunol.15.1.797","volume":"15","author":"T Taga","year":"1997","unstructured":"Taga, T. & Kishimoto, T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15, 797\u2013819, https:\/\/doi.org\/10.1146\/annurev.immunol.15.1.797 (1997).","journal-title":"Annu Rev Immunol"},{"key":"32007_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.imbio.2006.05.008","volume":"211","author":"D Ruckerl","year":"2006","unstructured":"Ruckerl, D., Hessmann, M., Yoshimoto, T., Ehlers, S. & Holscher, C. Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1. Immunobiology 211, 427\u2013436, https:\/\/doi.org\/10.1016\/j.imbio.2006.05.008 (2006).","journal-title":"Immunobiology"},{"key":"32007_CR7","doi-asserted-by":"publisher","first-page":"4886","DOI":"10.4049\/jimmunol.170.10.4886","volume":"170","author":"A Takeda","year":"2003","unstructured":"Takeda, A. et al. Cutting edge: role of IL-27\/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. The Journal of Immunology 170, 4886\u20134890 (2003).","journal-title":"The Journal of Immunology"},{"key":"32007_CR8","doi-asserted-by":"publisher","first-page":"6325","DOI":"10.4049\/jimmunol.180.9.6325","volume":"180","author":"GD Kalliolias","year":"2008","unstructured":"Kalliolias, G. D. & Ivashkiv, L. B. IL-27 activates human monocytes via STAT1 and suppresses IL-10 production but the inflammatory functions of IL-27 are abrogated by TLRs and p38. The Journal of Immunology 180, 6325\u20136333 (2008).","journal-title":"The Journal of Immunology"},{"key":"32007_CR9","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.bbrc.2007.12.154","volume":"367","author":"XM Feng","year":"2008","unstructured":"Feng, X. M. et al. Regulation of the class II and class I MHC pathways in human THP-1 monocytic cells by interleukin-27. Biochemical and Biophysical Research Communications 367, 553\u2013559 (2008).","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"32007_CR10","doi-asserted-by":"publisher","first-page":"24404","DOI":"10.1074\/jbc.M110.112599","volume":"285","author":"C Guzzo","year":"2010","unstructured":"Guzzo, C., Mat, N. F. C. & Gee, K. Interleukin-27 induces a STAT1\/3-and NF-\u03baB-dependent proinflammatory cytokine profile in human monocytes. Journal of Biological Chemistry 285, 24404\u201324411 (2010).","journal-title":"Journal of Biological Chemistry"},{"key":"32007_CR11","doi-asserted-by":"publisher","first-page":"864","DOI":"10.4049\/jimmunol.1101912","volume":"188","author":"C Guzzo","year":"2012","unstructured":"Guzzo, C., Ayer, A., Basta, S., Banfield, B. W. & Gee, K. IL-27 enhances LPS-induced proinflammatory cytokine production via upregulation of TLR4 expression and signaling in human monocytes. The Journal of Immunology 188, 864\u2013873 (2012).","journal-title":"The Journal of Immunology"},{"key":"32007_CR12","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1084\/jem.20120572","volume":"210","author":"L Dai","year":"2013","unstructured":"Dai, L. et al. IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation. The Journal of experimental medicine 210, 517\u2013534 (2013).","journal-title":"The Journal of experimental medicine"},{"key":"32007_CR13","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1189\/jlb.3A0316-098R","volume":"102","author":"C Petes","year":"2017","unstructured":"Petes, C. et al. IL-27 enhances LPS-induced IL-1beta in human monocytes and murine macrophages. J Leukoc Biol 102, 83\u201394, https:\/\/doi.org\/10.1189\/jlb.3A0316-098R (2017).","journal-title":"J Leukoc Biol"},{"key":"32007_CR14","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev.immunol.21.120601.141126","volume":"21","author":"K Takeda","year":"2003","unstructured":"Takeda, K., Kaisho, T. & Akira, S. Toll-like receptors. Annual review of immunology 21, 335\u2013376 (2003).","journal-title":"Annual review of immunology"},{"key":"32007_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/intimm\/dxh186","volume":"17","author":"K Takeda","year":"2005","unstructured":"Takeda, K. & Akira, S. Toll-like receptors in innate immunity. International immunology 17, 1\u201314 (2005).","journal-title":"International immunology"},{"key":"32007_CR16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","volume":"11","author":"T Kawai","year":"2010","unstructured":"Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature immunology 11, 373\u2013384 (2010).","journal-title":"Nature immunology"},{"key":"32007_CR17","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.imbio.2007.11.008","volume":"213","author":"MA Freudenberg","year":"2008","unstructured":"Freudenberg, M. A. et al. Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: benefits and hazards of LPS hypersensitivity. Immunobiology 213, 193\u2013203 (2008).","journal-title":"Immunobiology"},{"key":"32007_CR18","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/35074106","volume":"410","author":"F Hayashi","year":"2001","unstructured":"Hayashi, F., Smith, K. D., Ozinsky, A. & Hawn, T. R. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099 (2001).","journal-title":"Nature"},{"key":"32007_CR19","doi-asserted-by":"publisher","first-page":"5894","DOI":"10.4049\/jimmunol.164.11.5894","volume":"164","author":"CM Rosenberger","year":"2000","unstructured":"Rosenberger, C. M., Scott, M. G., Gold, M. R., Hancock, R. E. & Finlay, B. B. Salmonella typhimurium infection and lipopolysaccharide stimulation induce similar changes in macrophage gene expression. The Journal of Immunology 164, 5894\u20135904 (2000).","journal-title":"The Journal of Immunology"},{"key":"32007_CR20","doi-asserted-by":"publisher","first-page":"5445","DOI":"10.4049\/jimmunol.170.11.5445","volume":"170","author":"MC Royle","year":"2003","unstructured":"Royle, M. C., T\u00f6temeyer, S., Alldridge, L. C., Maskell, D. J. & Bryant, C. E. Stimulation of Toll-like receptor 4 by lipopolysaccharide during cellular invasion by live Salmonella typhimurium is a critical but not exclusive event leading to macrophage responses. The Journal of Immunology 170, 5445\u20135454 (2003).","journal-title":"The Journal of Immunology"},{"key":"32007_CR21","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.4049\/jimmunol.1500105","volume":"195","author":"DJ Perkins","year":"2015","unstructured":"Perkins, D. J. et al. Salmonella typhimurium co-opts the host type I IFN system to restrict macrophage innate immune transcriptional responses selectively. The Journal of Immunology 195, 2461\u20132471 (2015).","journal-title":"The Journal of Immunology"},{"key":"32007_CR22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1006\/mpat.2001.0448","volume":"31","author":"M Svensson","year":"2001","unstructured":"Svensson, M., Johansson, C. & Wick, M. J. Salmonella typhimurium-induced cytokine production and surface molecule expression by murine macrophages. Microbial pathogenesis 31, 91\u2013102 (2001).","journal-title":"Microbial pathogenesis"},{"key":"32007_CR23","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1126\/science.1085536","volume":"300","author":"GM Barton","year":"2003","unstructured":"Barton, G. M. & Medzhitov, R. Toll-like receptor signaling pathways. Science 300, 1524\u20131525 (2003).","journal-title":"Science"},{"key":"32007_CR24","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.molimm.2013.09.009","volume":"57","author":"D Kim","year":"2014","unstructured":"Kim, D. & Kim, J. Y. Anti-CD14 antibody reduces LPS responsiveness via TLR4 internalization in human monocytes. Molecular immunology 57, 210\u2013215 (2014).","journal-title":"Molecular immunology"},{"key":"32007_CR25","doi-asserted-by":"crossref","unstructured":"Jiang, Z. et al. CD14 is required for MyD88-independent LPS signaling. Nature immunology 6 (2005).","DOI":"10.1038\/ni1207"},{"key":"32007_CR26","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","volume":"42","author":"Y-C Lu","year":"2008","unstructured":"Lu, Y.-C., Yeh, W.-C. & Ohashi, P. S. LPS\/TLR4 signal transduction pathway. Cytokine 42, 145\u2013151 (2008).","journal-title":"Cytokine"},{"key":"32007_CR27","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1073\/pnas.1218080110","volume":"110","author":"BD Needham","year":"2013","unstructured":"Needham, B. D. et al. Modulating the innate immune response by combinatorial engineering of endotoxin. Proceedings of the National Academy of Sciences 110, 1464\u20131469 (2013).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"32007_CR28","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1128\/IAI.01705-14","volume":"82","author":"DL Jessen","year":"2014","unstructured":"Jessen, D. L. et al. Type III secretion needle proteins induce cell signaling and cytokine secretion via Toll-like receptors. Infection and immunity 82, 2300\u20132309 (2014).","journal-title":"Infection and immunity"},{"key":"32007_CR29","doi-asserted-by":"publisher","first-page":"5397","DOI":"10.4049\/jimmunol.1403009","volume":"194","author":"FC Hansen","year":"2015","unstructured":"Hansen, F. C. et al. The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through interactions with lipopolysaccharide and macrophages\/monocytes. The Journal of Immunology 194, 5397\u20135406 (2015).","journal-title":"The Journal of Immunology"},{"key":"32007_CR30","doi-asserted-by":"crossref","unstructured":"Na, B. H., Hoang, T. X. & Kim, J. Y. Hsp90 Inhibition Reduces TLR5 Surface Expression and NF-\u03baB Activation in Human Myeloid Leukemia THP-1Cells. BioMed Research International 2018 (2018).","DOI":"10.1155\/2018\/4319369"},{"key":"32007_CR31","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.placenta.2013.06.003","volume":"34","author":"T Nguyen","year":"2013","unstructured":"Nguyen, T. et al. IL-10 produced by trophoblast cells inhibits phagosome maturation leading to profound intracellular proliferation of Salmonella enterica Typhimurium. Placenta 34, 765\u2013774 (2013).","journal-title":"Placenta"},{"key":"32007_CR32","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1128\/IAI.73.5.2835-2840.2005","volume":"73","author":"E Valle","year":"2005","unstructured":"Valle, E. & Guiney, D. G. Characterization of Salmonella-induced cell death in human macrophage-like THP-1 cells. Infection and immunity 73, 2835\u20132840 (2005).","journal-title":"Infection and immunity"},{"key":"32007_CR33","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1099\/mic.0.032896-0","volume":"156","author":"JA Ibarra","year":"2010","unstructured":"Ibarra, J. A. et al. Induction of Salmonella pathogenicity island 1 under different growth conditions can affect Salmonella\u2013host cell interactions in vitro. Microbiology 156, 1120\u20131133 (2010).","journal-title":"Microbiology"},{"key":"32007_CR34","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1093\/intimm\/dxh247","volume":"17","author":"N Schuetze","year":"2005","unstructured":"Schuetze, N. et al. IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Int Immunol 17, 649\u2013659, https:\/\/doi.org\/10.1093\/intimm\/dxh247 (2005).","journal-title":"Int Immunol"},{"key":"32007_CR35","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1086\/589774","volume":"198","author":"CM Robinson","year":"2008","unstructured":"Robinson, C. M. & Nau, G. J. Interleukin-12 and interleukin-27 regulate macrophage control of Mycobacterium tuberculosis. The Journal of infectious diseases 198, 359\u2013366 (2008).","journal-title":"The Journal of infectious diseases"},{"key":"32007_CR36","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.cyto.2012.06.012","volume":"60","author":"CM Robinson","year":"2012","unstructured":"Robinson, C. M., Jung, J.-Y. & Nau, G. J. Interferon-\u03b3, tumor necrosis factor, and interleukin-18 cooperate to control growth of Mycobacterium tuberculosis in human macrophages. Cytokine 60, 233\u2013241 (2012).","journal-title":"Cytokine"},{"key":"32007_CR37","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/35038103","volume":"407","author":"Q Chen","year":"2000","unstructured":"Chen, Q., Ghilardi, N., Wang, H. & Baker, T. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407, 916 (2000).","journal-title":"Nature"},{"key":"32007_CR38","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/S1074-7613(01)00206-0","volume":"15","author":"H Yoshida","year":"2001","unstructured":"Yoshida, H. et al. WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity 15, 569\u2013578 (2001).","journal-title":"Immunity"},{"key":"32007_CR39","doi-asserted-by":"publisher","first-page":"3280","DOI":"10.1002\/eji.201242526","volume":"42","author":"D Rinchai","year":"2012","unstructured":"Rinchai, D. et al. Production of interleukin-27 by human neutrophils regulates their function during bacterial infection. Eur J Immunol 42, 3280\u20133290, https:\/\/doi.org\/10.1002\/eji.201242526 (2012).","journal-title":"Eur J Immunol"},{"key":"32007_CR40","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1111\/j.1365-2567.2009.03146.x","volume":"128","author":"S Talbot","year":"2009","unstructured":"Talbot, S. et al. Toll\u2010like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar Typhimurium infection, but not for the initiation of bacterial clearance. Immunology 128, 472\u2013483 (2009).","journal-title":"Immunology"},{"key":"32007_CR41","doi-asserted-by":"publisher","first-page":"12487","DOI":"10.1073\/pnas.0605200103","volume":"103","author":"V Feuillet","year":"2006","unstructured":"Feuillet, V. et al. Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proceedings of the National Academy of Sciences 103, 12487\u201312492 (2006).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"32007_CR42","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1128\/IAI.01491-07","volume":"76","author":"M Vijay-Kumar","year":"2008","unstructured":"Vijay-Kumar, M. et al. Toll-like receptor 5-deficient mice have dysregulated intestinal gene expression and nonspecific resistance to Salmonella-induced typhoid-like disease. Infection and immunity 76, 1276\u20131281 (2008).","journal-title":"Infection and immunity"},{"key":"32007_CR43","doi-asserted-by":"publisher","first-page":"13346","DOI":"10.1074\/jbc.M200149200","volume":"277","author":"KA Reed","year":"2002","unstructured":"Reed, K. A. et al. The Salmonella typhimurium flagellar basal body protein FliE is required for flagellin production and to induce a proinflammatory response in epithelial cells. Journal of Biological Chemistry 277, 13346\u201313353 (2002).","journal-title":"Journal of Biological Chemistry"},{"key":"32007_CR44","doi-asserted-by":"publisher","first-page":"6217","DOI":"10.4049\/jimmunol.170.12.6217","volume":"170","author":"SB Mizel","year":"2003","unstructured":"Mizel, S. B., Honko, A. N., Moors, M. A., Smith, P. S. & West, A. P. Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5\/Toll-like receptor 4 complexes. The Journal of Immunology 170, 6217\u20136223 (2003).","journal-title":"The Journal of Immunology"},{"key":"32007_CR45","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.imbio.2010.03.004","volume":"216","author":"S Hu","year":"2011","unstructured":"Hu, S., Wong, C. K. & Lam, C. W. K. Activation of eosinophils by IL-12 family cytokine IL-27: Implications of the pleiotropic roles of IL-27 in allergic responses. Immunobiology 216, 54\u201365 (2011).","journal-title":"Immunobiology"},{"key":"32007_CR46","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.imbio.2017.01.002","volume":"222","author":"M Xu","year":"2017","unstructured":"Xu, M. et al. Treponema pallidum flagellins elicit proinflammatory cytokines from human monocytes via TLR5 signaling pathway. Immunobiology 222, 709\u2013718 (2017).","journal-title":"Immunobiology"},{"key":"32007_CR47","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.imlet.2011.01.001","volume":"136","author":"H-Y Cho","year":"2011","unstructured":"Cho, H.-Y. et al. All-trans retinoic acid induces TLR-5 expression and cell differentiation and promotes flagellin-mediated cell functions in human THP-1 cells. Immunology letters 136, 97\u2013107 (2011).","journal-title":"Immunology letters"},{"key":"32007_CR48","doi-asserted-by":"publisher","first-page":"G467","DOI":"10.1152\/ajpgi.00364.2009","volume":"299","author":"KT Chen","year":"2010","unstructured":"Chen, K. T. et al. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. American Journal of Physiology-Gastrointestinal and Liver Physiology 299, G467\u2013G475 (2010).","journal-title":"American Journal of Physiology-Gastrointestinal and Liver Physiology"},{"key":"32007_CR49","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.1462-5822.2005.00621.x","volume":"8","author":"M Bachmann","year":"2006","unstructured":"Bachmann, M. et al. Interleukin\u201018 secretion and Th1\u2010like cytokine responses in human peripheral blood mononuclear cells under the influence of the toll\u2010like receptor\u20105 ligand flagellin. Cellular microbiology 8, 289\u2013300 (2006).","journal-title":"Cellular microbiology"},{"key":"32007_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/2050-7771-2-1","volume":"2","author":"J Yang","year":"2014","unstructured":"Yang, J., Zhang, L., Yu, C., Yang, X. F. & Wang, H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomarker research 2, 1, https:\/\/doi.org\/10.1186\/2050-7771-2-1 (2014).","journal-title":"Biomarker research"},{"key":"32007_CR51","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1182\/blood-2010-02-258558","volume":"116","author":"L Ziegler-Heitbrock","year":"2010","unstructured":"Ziegler-Heitbrock, L. et al. Nomenclature of monocytes and dendritic cells in blood. Blood 116, e74\u201380, https:\/\/doi.org\/10.1182\/blood-2010-02-258558 (2010).","journal-title":"Blood"},{"key":"32007_CR52","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1146\/annurev.immunol.26.021607.090326","volume":"26","author":"NV Serbina","year":"2008","unstructured":"Serbina, N. V., Jia, T., Hohl, T. M. & Pamer, E. G. Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26, 421\u2013452, https:\/\/doi.org\/10.1146\/annurev.immunol.26.021607.090326 (2008).","journal-title":"Annu Rev Immunol"},{"key":"32007_CR53","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1159\/000330771","volume":"3","author":"MJ Wick","year":"2011","unstructured":"Wick, M. J. Innate immune control of Salmonella enterica serovar Typhimurium: mechanisms contributing to combating systemic Salmonella infection. Journal of innate immunity 3, 543\u2013549, https:\/\/doi.org\/10.1159\/000330771 (2011).","journal-title":"Journal of innate immunity"},{"key":"32007_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-8-1","volume":"8","author":"O Sharif","year":"2007","unstructured":"Sharif, O., Bolshakov, V. N., Raines, S., Newham, P. & Perkins, N. D. Transcriptional profiling of the LPS induced NF-\u03baB response in macrophages. BMC immunology 8, 1 (2007).","journal-title":"BMC immunology"},{"key":"32007_CR55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.atherosclerosis.2011.09.003","volume":"221","author":"Z Qin","year":"2012","unstructured":"Qin, Z. The use of THP-1 cells as a model for mimicking the function and regulation of monocytes and macrophages in the vasculature. Atherosclerosis 221, 2\u201311 (2012).","journal-title":"Atherosclerosis"},{"key":"32007_CR56","doi-asserted-by":"crossref","unstructured":"Schildberger, A., Rossmanith, E., Eichhorn, T., Strassl, K. & Weber, V. Monocytes, peripheral blood mononuclear cells, and THP-1 cells exhibit different cytokine expression patterns following stimulation with lipopolysaccharide. Mediators of inflammation 2013 (2013).","DOI":"10.1155\/2013\/697972"},{"key":"32007_CR57","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/BF02041244","volume":"47","author":"J Auwerx","year":"1991","unstructured":"Auwerx, J. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Experientia 47, 22\u201331 (1991).","journal-title":"Experientia"},{"key":"32007_CR58","doi-asserted-by":"crossref","first-page":"5176","DOI":"10.1128\/IAI.67.10.5176-5185.1999","volume":"67","author":"F Ciacci-Woolwine","year":"1999","unstructured":"Ciacci-Woolwine, F., McDermott, P. F. & Mizel, S. B. Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes. Infect Immun 67, 5176\u20135185 (1999).","journal-title":"Infect Immun"},{"key":"32007_CR59","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.immuni.2012.06.014","volume":"37","author":"AO Hall","year":"2012","unstructured":"Hall, A. O. et al. The cytokines interleukin 27 and interferon-gamma promote distinct Treg cell populations required to limit infection-induced pathology. Immunity 37, 511\u2013523, https:\/\/doi.org\/10.1016\/j.immuni.2012.06.014 (2012).","journal-title":"Immunity"},{"key":"32007_CR60","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1002\/eji.200324815","volume":"34","author":"HH Smits","year":"2004","unstructured":"Smits, H. H. et al. Commensal Gram\u2010negative bacteria prime human dendritic cells for enhanced IL\u201023 and IL\u201027 expression and enhanced Th1 development. European journal of immunology 34, 1371\u20131380 (2004).","journal-title":"European journal of immunology"},{"key":"32007_CR61","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.imbio.2007.09.004","volume":"212","author":"S Siegemund","year":"2007","unstructured":"Siegemund, S. et al. Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS\/TLR4-dependent induction by Salmonella Enteritidis. Immunobiology 212, 739\u2013750, https:\/\/doi.org\/10.1016\/j.imbio.2007.09.004 (2007).","journal-title":"Immunobiology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32007-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32007-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32007-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T09:35:14Z","timestamp":1671615314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32007-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,12]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["32007"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-32007-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,12]]},"assertion":[{"value":"23 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"13704"}}