{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T22:53:46Z","timestamp":1783810426505,"version":"3.55.0"},"reference-count":68,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T00:00:00Z","timestamp":1571097600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:p>\n                    The potency of synthetic CpG-oligo-deoxynucleotides (CpG-ODNs) adjuvants in modulating the immune cell functions through the TLR pathway has been tested and reported previously. However, the cellular signaling involved in the stimulation of macrophages by natural, CpG motif-containing adjuvant and the effector functions modulated by such stimulation has not been well studied. Here, we used in vitro and ex vivo murine macrophage assay systems, and mouse model of in vivo stimulation to explore the signaling pathway and the effector functions mediated by BC01. Results show that BC01 can induce the production of TNF-\u03b1 and MCP-1 in macrophages by up-regulating the activation of NF-\u03baB and MAPKs signaling pathway, and elevated the expression of MHC-II, CD40, CD80, and CD86. Upon stimulation with BC01, the peritoneal macrophages isolated from TLR9\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice produced significantly low levels of pro-inflammatory cytokines, attenuated the activation of NF-\u03baB and MAPKs signaling pathways, and showed reduced phagocytosis. Following in vivo stimulation with BC01, the TLR9\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice produced significantly lower levels of pro-inflammatory cytokines in the serum and lymph nodes showed reduced cell proliferation. These results indicate that BC01 is an efficient agonist of TLR9 that can significantly enhance the host-protective immune functions of macrophages.\n                  <\/jats:p>","DOI":"10.1177\/1753425919879997","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T02:43:46Z","timestamp":1571193826000},"page":"183-203","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Unmethylated CpG motif-containing genomic DNA fragment of\n                    <i>Bacillus calmette-guerin<\/i>\n                    promotes macrophage functions through TLR9-mediated activation of NF-\n                    <b>\u03ba<\/b>\n                    B and MAPKs signaling pathways"],"prefix":"10.1177","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-3375","authenticated-orcid":false,"given":"Junli","family":"Li","sequence":"first","affiliation":[{"name":"Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China"},{"name":"NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, P.R. China"},{"name":"Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, P.R. China"},{"name":"Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing, P.R. China"},{"name":"Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS), Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvakumar","family":"Subbian","sequence":"additional","affiliation":[{"name":"Public Health Research Institute (PHRI) center at New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, P.R. China"},{"name":"Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, P.R. China"},{"name":"Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine, Beijing, P.R. China"},{"name":"Tuberculosis Center, Chinese Academy of Medical Sciences (CAMS), Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"bibr1-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.003"},{"key":"bibr2-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091181"},{"key":"bibr3-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.02.009"},{"key":"bibr4-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-8-37"},{"key":"bibr5-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/41131"},{"key":"bibr6-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/35021228"},{"key":"bibr7-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11837"},{"key":"bibr8-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"bibr9-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/ni1112"},{"key":"bibr10-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.07.010"},{"key":"bibr11-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.006"},{"key":"bibr12-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.005015"},{"key":"bibr13-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.002"},{"key":"bibr14-1753425919879997","doi-asserted-by":"publisher","DOI":"10.2217\/imt.09.70"},{"key":"bibr15-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8228-6"},{"key":"bibr16-1753425919879997","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901474"},{"key":"bibr17-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/374546a0"},{"key":"bibr18-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2059"},{"key":"bibr19-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2007.12.004"},{"key":"bibr20-1753425919879997","doi-asserted-by":"publisher","DOI":"10.2165\/11536140-000000000-00000"},{"key":"bibr21-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.012"},{"key":"bibr22-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1999.1572"},{"key":"bibr23-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2000.107927"},{"key":"bibr24-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.016"},{"key":"bibr25-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38294"},{"key":"bibr26-1753425919879997","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3339"},{"key":"bibr27-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/35100529"},{"key":"bibr28-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2541"},{"key":"bibr29-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/nri1703"},{"key":"bibr30-1753425919879997","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.4049\/jimmunol.156.12.4867","volume":"156","author":"Nick JA","year":"1996","journal-title":"J Immunol"},{"key":"bibr31-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/372739a0"},{"key":"bibr32-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00365.2009"},{"key":"bibr33-1753425919879997","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002739"},{"key":"bibr34-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.10.004"},{"key":"bibr35-1753425919879997","first-page":"356","volume":"5","author":"Zhao AH","year":"2007","journal-title":"Chin J Biol"},{"key":"bibr36-1753425919879997","first-page":"94","volume":"2","author":"Zhao AH","year":"2010","journal-title":"Chin Med Biotechnol"},{"key":"bibr37-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2010.00660.x"},{"key":"bibr38-1753425919879997","first-page":"1177","volume":"24","author":"Zhang Y","year":"2011","journal-title":"Chin J Biol"},{"key":"bibr39-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2012.12.015"},{"key":"bibr40-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410868200"},{"key":"bibr41-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400476"},{"key":"bibr42-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164860"},{"key":"bibr43-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.649"},{"key":"bibr44-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225"},{"key":"bibr45-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"bibr46-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"bibr47-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26448"},{"key":"bibr48-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.43.30353"},{"key":"bibr49-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062374"},{"key":"bibr50-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/nm1201-1291"},{"key":"bibr51-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110572200"},{"key":"bibr52-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.012"},{"key":"bibr53-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2004.04.009"},{"key":"bibr54-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-061008-103129"},{"key":"bibr55-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1586\/erv.10.174"},{"key":"bibr56-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1159\/000142731"},{"key":"bibr57-1753425919879997","first-page":"955","volume":"72","author":"Tokunaga T","year":"1984","journal-title":"J Natl Cancer Inst"},{"key":"bibr58-1753425919879997","first-page":"681","volume":"74","author":"Shimada S","year":"1985","journal-title":"J Natl Cancer Inst"},{"key":"bibr59-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.6.2236-2242.1995"},{"key":"bibr60-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-010-9197-0"},{"key":"bibr61-1753425919879997","first-page":"39","volume":"186","author":"Cooper A","year":"1997","journal-title":"Mycobacterium tuberculosis"},{"key":"bibr62-1753425919879997","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3339"},{"key":"bibr63-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-014-0077-5"},{"key":"bibr64-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.5.2686-2696.2006"},{"key":"bibr65-1753425919879997","first-page":"270","volume":"4","author":"Tino MJ","year":"1996","journal-title":"Am J Physiol-Lung C"},{"key":"bibr66-1753425919879997","doi-asserted-by":"publisher","DOI":"10.1038\/44605"},{"key":"bibr67-1753425919879997","doi-asserted-by":"crossref","unstructured":"M. Bartl M, Luckenbach T, Bergner O, et\u00a0al.  Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes. 2001;  271: 130\u2013141.","DOI":"10.1006\/excr.2001.5358"},{"key":"bibr68-1753425919879997","first-page":"574","volume":"19","author":"Zhao AH","year":"2006","journal-title":"Chin J Biol"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425919879997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1753425919879997","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1753425919879997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:02:59Z","timestamp":1777460579000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1753425919879997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,15]]},"references-count":68,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1177\/1753425919879997"],"URL":"https:\/\/doi.org\/10.1177\/1753425919879997","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,15]]}}}