{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:28:57Z","timestamp":1793118537815,"version":"4.5.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella abortus<\/jats:named-content>is an intracellular pathogen that uses a crafty strategy to invade and proliferate within host cells, but the distinct signaling pathways associated with phagocytic mechanisms of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>remain unclear. The present study was performed to test the hypothesis that Toll-like receptor 4 (TLR4)-linked signaling interacting with Janus kinase 2 (JAK2) plays an essential role in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>phagocytosis by macrophages. The effects of TLR4-JAK2 signaling on<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>phagocytosis in murine macrophage RAW 264.7 cells were observed through an infection assay and confocal microscopy. We determined that the uptake of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>was negatively affected by the dysfunction of TLR4 and JAK2. F-actin polymerization detected by flow cytometry and F-actin assay was amplified for<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>entry, whereas that event was attenuated by the disruption of TLR4 and JAK2. Importantly, JAK2 phosphorylation and actin skeleton reorganization were suppressed immediately after<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>infection in bone marrow-derived macrophages (BMDMs) from TLR4<jats:sup>\u2212\/\u2212<\/jats:sup>mice, showing the cooperation of JAK2 with TLR4. Furthermore, small GTPase Cdc42 participated in the intermediate pathway of TLR4-JAK2 signaling on<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>phagocytosis. Consequently, TLR4-associated JAK2 activation in the early cellular signaling events plays a pivotal role in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>-induced phagocytic processes in macrophages, implying the pathogenic significance of JAK2-mediated entry. Here, we elucidate that this specific phagocytic mechanism of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>might provide achievable strategies for inhibiting<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>invasion.<\/jats:p>","DOI":"10.1128\/iai.00403-13","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T04:03:46Z","timestamp":1367294626000},"page":"2448-2458","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Toll-Like Receptor 4-Linked Janus Kinase 2 Signaling Contributes to Internalization of Brucella abortus by Macrophages"],"prefix":"10.1128","volume":"81","author":[{"given":"Jin Ju","family":"Lee","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyeok","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu Jang","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wongi","family":"Min","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Hee","family":"Rhee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"School of Life Science and Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahisa","family":"Watarai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Public Health, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea"},{"name":"Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Zoonoses and communicable diseases common to man and animals","author":"Acha P","year":"1980","unstructured":"AchaPSzylresB. 1980. Zoonoses and communicable diseases common to man and animals. Pan American Health Organization, Washington, DC."},{"key":"e_1_3_3_3_2","first-page":"363","article-title":"Macrophages and Brucella","volume":"60","author":"Baldwin CL","year":"1994","unstructured":"BaldwinCLWinterAJ. 1994. Macrophages and Brucella. Immunol. Ser. 60:363\u2013380.","journal-title":"Immunol. Ser"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.7.2320-2328.1990"},{"key":"e_1_3_3_5_2","first-page":"197","article-title":"Interactions between professional phagocytes and Brucella spp","volume":"12","author":"Liautard JP","year":"1996","unstructured":"LiautardJPGrossADornandJKohlerS. 1996. Interactions between professional phagocytes and Brucella spp. Microbiologia 12:197\u2013206.","journal-title":"Microbiologia"},{"key":"e_1_3_3_6_2","first-page":"207","article-title":"Molecular basis of Brucella pathogenicity: an update","volume":"12","author":"Sangari FJ","year":"1996","unstructured":"SangariFJAgueroJ. 1996. Molecular basis of Brucella pathogenicity: an update. Microbiologia 12:207\u2013218.","journal-title":"Microbiologia"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01603"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098588802500104"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00195.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105606200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.2460\/ajvr.1991.52.10.1658","article-title":"Effect of endocytic and metabolic inhibitors on the internalization and intracellular growth of Brucella abortus in Vero cells","volume":"52","author":"Detilleux PG","year":"1991","unstructured":"DetilleuxPGDeyoeBLChevilleNF. 1991. Effect of endocytic and metabolic inhibitors on the internalization and intracellular growth of Brucella abortus in Vero cells. Am. J. Vet. Res. 52:1658\u20131664.","journal-title":"Am. J. Vet. Res"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.2000.0354"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.2110-2119.2003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.07.005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3310489"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02481-4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203925"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208788"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00754.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-010-0628-z"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-8244(03)00231-1"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(02)00515-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00115-X"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.01.005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02193.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.19.13198"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101103200"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031237"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5508.1544"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250476497"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1068"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxl119"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2011.0274"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00026.2003"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901031"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2007.12.002"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003324"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096158"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.3070"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.65"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.176-186.2004"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000631"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.5137-5143.2005"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.4049\/jimmunol.0902209","article-title":"The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis","volume":"184","author":"Pasquevich KA","year":"2010","unstructured":"PasquevichKAGarcia SamartinoCCoriaLMEsteinSMZwerdlingAIbanezAEBarrionuevoPOliveiraFSCarvalhoNBBorkowskiJOliveiraSCWarzechaHGiambartolomeiGHCassataroJ. 2010. The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. J. Immunol. 184:5200\u20135212.","journal-title":"J. Immunol"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-43-29"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/518323"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3109\/08923979609052736"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.509"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5394.1717"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.9.1487"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.4.1316-1333.2003"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1206763"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00403-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00403-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T16:52:55Z","timestamp":1715273575000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00403-13"}},"subtitle":[],"editor":[{"given":"S. R.","family":"Blanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":53,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1128\/IAI.00403-13"],"URL":"https:\/\/doi.org\/10.1128\/iai.00403-13","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7]]},"assertion":[{"value":"2013-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}