{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:30:39Z","timestamp":1792103439995,"version":"4.4.0"},"reference-count":101,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T00:00:00Z","timestamp":1576195200000},"content-version":"vor","delay-in-days":1656,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases Western Regional Center of Excellence","award":["1U54 AI057156-01"],"award-info":[{"award-number":["1U54 AI057156-01"]}]},{"name":"US Department of Homeland Security National Center of Excellence","award":["ONR-N00014-04-1-0"],"award-info":[{"award-number":["ONR-N00014-04-1-0"]}]},{"DOI":"10.13039\/100000005","name":"US Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-10-1-125"],"award-info":[{"award-number":["W81XWH-10-1-125"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.jp","journals.elsevierhealth.com","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Pathology"],"published-print":{"date-parts":[[2015,6]]},"DOI":"10.1016\/j.ajpath.2015.03.003","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T21:34:00Z","timestamp":1429306440000},"page":"1505-1517","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":455,"title":["Pathogenesis and Immunobiology of Brucellosis"],"prefix":"10.1016","volume":"185","author":[{"given":"Paul","family":"de Figueiredo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Ficht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Rice-Ficht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Rossetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Garry","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajpath.2015.03.003_bib1","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1007\/s00018-006-6311-4","article-title":"Brucella as a biological weapon","volume":"63","author":"Pappas","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.ajpath.2015.03.003_bib2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/j.humpath.2014.07.007","article-title":"Liver histology of acute brucellosis caused by Brucella melitensis","volume":"45","author":"Young","year":"2014","journal-title":"Hum Pathol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib3","doi-asserted-by":"crossref","first-page":"e1929","DOI":"10.1371\/journal.pntd.0001929","article-title":"Clinical manifestations of human brucellosis: a systematic review and meta-analysis","volume":"6","author":"Dean","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"10.1016\/j.ajpath.2015.03.003_bib4","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2217\/fmb.12.140","article-title":"Brucella evasion of adaptive immunity","volume":"8","author":"Martirosyan","year":"2013","journal-title":"Future Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib5","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1111\/j.1469-0691.2011.03604.x","article-title":"Intracellular bacteria and adverse pregnancy outcomes","volume":"17","author":"Baud","year":"2011","journal-title":"Clin Microbiol Infect"},{"key":"10.1016\/j.ajpath.2015.03.003_bib6","doi-asserted-by":"crossref","first-page":"e81719","DOI":"10.1371\/journal.pone.0081719","article-title":"Systems biology analysis of Brucella infected Peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome","volume":"8","author":"Rossetti","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2015.03.003_bib7","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0378-1135(02)00235-3","article-title":"The pathology of brucellosis reflects the outcome of the battle between the host genome and the Brucella genome","volume":"90","author":"Adams","year":"2002","journal-title":"Vet Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib8","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.micinf.2012.03.003","article-title":"Transcriptome analysis of HeLa cells response to Brucella melitensis infection: a molecular approach to understand the role of the mucosal epithelium in the onset of the Brucella pathogenesis","volume":"14","author":"Rossetti","year":"2012","journal-title":"Microbes Infect"},{"key":"10.1016\/j.ajpath.2015.03.003_bib9","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1462-5822.2004.00372.x","article-title":"Adherence of Brucella to human epithelial cells and macrophages is mediated by sialic acid residues","volume":"6","author":"Castaneda-Rold\u00e1n","year":"2004","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib10","doi-asserted-by":"crossref","first-page":"e631","DOI":"10.1371\/journal.pone.0000631","article-title":"Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection","volume":"2","author":"Barquero-Calvo","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2015.03.003_bib11","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.micinf.2008.07.005","article-title":"The role of innate immune receptors in the control of Brucella abortus infection: toll-like receptors and beyond","volume":"10","author":"Oliveira","year":"2008","journal-title":"Microbes Infect"},{"key":"10.1016\/j.ajpath.2015.03.003_bib12","doi-asserted-by":"crossref","first-page":"15711","DOI":"10.1073\/pnas.232454299","article-title":"The analysis of the intramacrophagic virulome of Brucella suis deciphers the environment encountered by the pathogen inside the macrophage host cell","volume":"99","author":"Kohler","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2015.03.003_bib13","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1021\/pr800978p","article-title":"Intracellular adaptation of Brucella abortus","volume":"8","author":"Lamontagne","year":"2009","journal-title":"J Proteome Res"},{"key":"10.1016\/j.ajpath.2015.03.003_bib14","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1111\/j.1462-5822.2007.00922.x","article-title":"Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice","volume":"9","author":"Roux","year":"2007","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib15","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1128\/JB.01915-07","article-title":"Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the Type IV secretion system and flagella","volume":"190","author":"Rambow-Larsen","year":"2008","journal-title":"J Bacteriol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/1471-2180-10-167","article-title":"Brucella melitensis VjbR and C12-HSL regulons: contributions of the N-dodecanoyl homoserine lactone signaling molecule and LuxR homologue VjbR to gene expression","volume":"10","author":"Weeks","year":"2010","journal-title":"BMC Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib17","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1128\/IAI.00637-07","article-title":"Brucella suis prevents human dendritic cell maturation and antigen presentation through regulation of tumor necrosis factor alpha secretion","volume":"75","author":"Billard","year":"2007","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib18","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1128\/IAI.01554-07","article-title":"Modulation of the bovine trophoblastic innate immune response by Brucella abortus","volume":"76","author":"Carvalho Neta","year":"2008","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib19","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1128\/IAI.01259-08","article-title":"Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte interaction upon infection with Brucella spp","volume":"77","author":"Delpino","year":"2009","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib20","doi-asserted-by":"crossref","first-page":"e1003785","DOI":"10.1371\/journal.ppat.1003785","article-title":"Brucella induces an unfolded protein response via TcpB that supports intracellular replication in macrophages","volume":"9","author":"Smith","year":"2013","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib21","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1462-5822.2001.00102.x","article-title":"Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole","volume":"3","author":"Comerci","year":"2001","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib22","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1046\/j.1462-5822.2001.00131.x","article-title":"Identification of Brucella spp. genes involved in intracellular trafficking","volume":"3","author":"Delrue","year":"2001","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib23","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/cmi.12224","article-title":"Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival","volume":"16","author":"Dohmer","year":"2014","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib24","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fcimb.2013.00028","article-title":"BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions","volume":"3","author":"Salcedo","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib25","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/j.1462-5822.2011.01601.x","article-title":"Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2","volume":"13","author":"de Barsy","year":"2011","journal-title":"Cell Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1084\/jem.20021980","article-title":"Cellular prion protein promotes Brucella infection into macrophages","volume":"198","author":"Watarai","year":"2003","journal-title":"J Exp Med"},{"key":"10.1016\/j.ajpath.2015.03.003_bib27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.micpath.2004.04.002","article-title":"Lipid raft microdomains mediate class A scavenger receptor-dependent infection of Brucella abortus","volume":"37","author":"Kim","year":"2004","journal-title":"Microb Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib28","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/ni1202","article-title":"Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival","volume":"6","author":"Arellano-Reynoso","year":"2005","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbrc.2011.11.104","article-title":"The Brucella TIR-like protein TcpB interacts with the death domain of MyD88","volume":"417","author":"Chaudhary","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib30","doi-asserted-by":"crossref","first-page":"956","DOI":"10.4049\/jimmunol.0902008","article-title":"Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL","volume":"184","author":"Sengupta","year":"2010","journal-title":"J Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib31","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00418-12","article-title":"Sensing of bacterial type IV secretion via the unfolded protein response","volume":"4","author":"de Jong","year":"2013","journal-title":"MBio"},{"key":"10.1016\/j.ajpath.2015.03.003_bib32","doi-asserted-by":"crossref","first-page":"e10216","DOI":"10.1371\/journal.pone.0010216","article-title":"Transcriptome analysis of the Brucella abortus BvrR\/BvrS two-component regulatory system","volume":"5","author":"Viadas","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2015.03.003_bib33","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1128\/IAI.00439-07","article-title":"BvrR\/BvrS-controlled outer membrane proteins Omp3a and Omp3b are not essential for Brucella abortus virulence","volume":"75","author":"Manterola","year":"2007","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0378-1135(02)00216-X","article-title":"Discovery of Brucella virulence mechanisms using mutational analysis","volume":"90","author":"Ficht","year":"2002","journal-title":"Vet Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0966-842X(03)00078-7","article-title":"What is the nature of the replicative niche of a stealthy bug named Brucella?","volume":"11","author":"Kohler","year":"2003","journal-title":"Trends Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib36","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1128\/IAI.72.1.176-186.2004","article-title":"Role of Toll-like receptor 4 in induction of cell-mediated immunity and resistance to Brucella abortus infection in mice","volume":"72","author":"Campos","year":"2004","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib37","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1128\/IAI.68.7.4102-4107.2000","article-title":"Identification of genes required for chronic persistence of Brucella abortus in mice","volume":"68","author":"Hong","year":"2000","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib38","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1046\/j.1365-2958.1999.01569.x","article-title":"A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis","volume":"33","author":"O'Callaghan","year":"1999","journal-title":"Mol Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib39","doi-asserted-by":"crossref","first-page":"e1003556","DOI":"10.1371\/journal.ppat.1003556","article-title":"Brucella modulates secretory trafficking via multiple type IV secretion effector proteins","volume":"9","author":"Myeni","year":"2013","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib40","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/415092a","article-title":"IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA","volume":"415","author":"Calfon","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.ajpath.2015.03.003_bib41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.immuni.2004.06.010","article-title":"XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation","volume":"21","author":"Shaffer","year":"2004","journal-title":"Immunity"},{"key":"10.1016\/j.ajpath.2015.03.003_bib42","doi-asserted-by":"crossref","first-page":"e1000110","DOI":"10.1371\/journal.ppat.1000110","article-title":"RNAi screen of endoplasmic reticulum-associated host factors reveals a role for IRE1alpha in supporting Brucella replication","volume":"4","author":"Qin","year":"2008","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.chom.2011.12.002","article-title":"Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle","volume":"11","author":"Starr","year":"2012","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.ajpath.2015.03.003_bib44","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1016\/j.febslet.2013.09.007","article-title":"Structure of the Toll\/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA\/Btp1\/TcpB","volume":"587","author":"Kaplan-Turkoz","year":"2013","journal-title":"FEBS Lett"},{"key":"10.1016\/j.ajpath.2015.03.003_bib45","doi-asserted-by":"crossref","first-page":"9892","DOI":"10.1074\/jbc.M805458200","article-title":"Brucella TIR domain-containing protein mimics properties of the Toll-like receptor adaptor protein TIRAP","volume":"284","author":"Radhakrishnan","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2015.03.003_bib46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1752-0509-5-7","article-title":"BiologicalNetworks\u2013tools enabling the integration of multi-scale data for the host-pathogen studies","volume":"5","author":"Kozhenkov","year":"2011","journal-title":"BMC Syst Biol"},{"issue":"Suppl 3","key":"10.1016\/j.ajpath.2015.03.003_bib47","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1752-0509-6-S3-S1","article-title":"Advances in systems biology: computational algorithms and applications","volume":"6","author":"Huang","year":"2012","journal-title":"BMC Syst Biol"},{"issue":"Suppl 2","key":"10.1016\/j.ajpath.2015.03.003_bib48","doi-asserted-by":"crossref","first-page":"I1","DOI":"10.1186\/1752-0509-8-S2-I1","article-title":"Data integration in the era of omics: current and future challenges","volume":"8","author":"Gomez-Cabrero","year":"2014","journal-title":"BMC Syst Biol"},{"issue":"Suppl 2","key":"10.1016\/j.ajpath.2015.03.003_bib49","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1752-0509-8-S2-S1","article-title":"The common ground of genomics and systems biology","volume":"8","author":"Conesa","year":"2014","journal-title":"BMC Syst Biol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib50","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1128\/IAI.68.3.1297-1303.2000","article-title":"Identification of Brucella suis genes affecting intracellular survival in an in\u00a0vitro human macrophage infection model by signature-tagged transposon mutagenesis","volume":"68","author":"Foulongne","year":"2000","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib51","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1128\/CMR.16.1.65-78.2003","article-title":"Molecular host-pathogen interaction in brucellosis: current understanding and future approaches to vaccine development for mice and humans","volume":"16","author":"Ko","year":"2003","journal-title":"Clin Microbiol Rev"},{"key":"10.1016\/j.ajpath.2015.03.003_bib52","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1073\/pnas.221575398","article-title":"The genome sequence of the facultative intracellular pathogen Brucella melitensis","volume":"99","author":"DelVecchio","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2015.03.003_bib53","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fcimb.2012.00002","article-title":"Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics","volume":"2","author":"He","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3727\/105221610X12819686555051","article-title":"Emerging roles for XBP1, a sUPeR transcription factor","volume":"15","author":"He","year":"2010","journal-title":"Gene Expr"},{"key":"10.1016\/j.ajpath.2015.03.003_bib55","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/1756-0500-3-244","article-title":"Selective amplification of Brucella melitensis mRNA from a mixed host-pathogen total RNA","volume":"3","author":"Rossetti","year":"2010","journal-title":"BMC Res Notes"},{"key":"10.1016\/j.ajpath.2015.03.003_bib56","doi-asserted-by":"crossref","first-page":"13906","DOI":"10.1074\/jbc.M113.459305","article-title":"The Brucella abortus general stress response system regulates chronic mammalian infection and is controlled by phosphorylation and proteolysis","volume":"288","author":"Kim","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ajpath.2015.03.003_bib57","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.micpath.2012.02.001","article-title":"Deep sequencing-based expression transcriptional profiling changes during Brucella infection","volume":"52","author":"Liu","year":"2012","journal-title":"Microb Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2041-1480-2-9","article-title":"Brucellosis Ontology (IDOBRU) as an extension of the Infectious Disease Ontology","volume":"2","author":"Lin","year":"2011","journal-title":"J Biomed Semantics"},{"key":"10.1016\/j.ajpath.2015.03.003_bib59","doi-asserted-by":"crossref","first-page":"e28485","DOI":"10.1371\/journal.pone.0028485","article-title":"Deep-sequencing analysis of the mouse transcriptome response to infection with Brucella melitensis strains of differing virulence","volume":"6","author":"Wang","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2015.03.003_bib60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S146625230700117X","article-title":"Brucella: functional genomics and host-pathogen interactions","volume":"7","author":"Rajashekara","year":"2006","journal-title":"Anim Health Res Rev"},{"issue":"Suppl 4","key":"10.1016\/j.ajpath.2015.03.003_bib61","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/1753-6561-5-S4-S6","article-title":"Multi-comparative systems biology analysis reveals time-course biosignatures of in\u00a0vivo bovine pathway responses to B.melitensis, S.enterica Typhimurium and M.avium paratuberculosis","volume":"5","author":"Adams","year":"2011","journal-title":"BMC Proc"},{"issue":"Suppl 1","key":"10.1016\/j.ajpath.2015.03.003_bib62","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1745-7580-6-S1-S5","article-title":"Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN","volume":"6","author":"He","year":"2010","journal-title":"Immunome Res"},{"key":"10.1016\/j.ajpath.2015.03.003_bib63","doi-asserted-by":"crossref","first-page":"e59751","DOI":"10.1371\/journal.pone.0059751","article-title":"Immunogenic and invasive properties of Brucella melitensis 16M outer membrane protein vaccine candidates identified via a reverse vaccinology approach","volume":"8","author":"Gomez","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ajpath.2015.03.003_bib64","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1186\/1471-2164-14-459","article-title":"Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses","volume":"14","author":"Hanna","year":"2013","journal-title":"BMC Genomics"},{"key":"10.1016\/j.ajpath.2015.03.003_bib65","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1016\/j.vaccine.2011.05.080","article-title":"Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development","volume":"29","author":"Adams","year":"2011","journal-title":"Vaccine"},{"key":"10.1016\/j.ajpath.2015.03.003_bib66","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fcimb.2013.00017","article-title":"Host-Brucella interactions and the Brucella genome as tools for subunit antigen discovery and immunization against brucellosis","volume":"3","author":"Gomez","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib67","doi-asserted-by":"crossref","first-page":"5137","DOI":"10.1128\/IAI.73.8.5137-5143.2005","article-title":"MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus","volume":"73","author":"Weiss","year":"2005","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib68","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/CVI.05321-11","article-title":"Extended safety and efficacy studies of the attenuated Brucella vaccine candidates 16 M(Delta)vjbR and S19(Delta)vjbR in the immunocompromised IRF-1-\/- mouse model","volume":"19","author":"Arenas-Gamboa","year":"2012","journal-title":"Clin Vaccine Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib69","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0378-1135(02)00225-0","article-title":"Molecular and cellular interactions between Brucella abortus antigens and host immune responses","volume":"90","author":"Oliveira","year":"2002","journal-title":"Vet Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib70","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1128\/IAI.63.10.4029-4033.1995","article-title":"Lack of a role for natural killer cells in early control of Brucella abortus 2308 infections in mice","volume":"63","author":"Fernandes","year":"1995","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib71","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.4049\/jimmunol.143.10.3330","article-title":"Temporal development of protective cell-mediated and humoral immunity in BALB\/c mice infected with Brucella abortus","volume":"143","author":"Araya","year":"1989","journal-title":"J Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib72","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1128\/IAI.53.2.245-251.1986","article-title":"Comparison of living and nonliving vaccines for Brucella abortus in BALB\/c mice","volume":"53","author":"Montaraz","year":"1986","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib73","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1128\/IAI.51.3.961-963.1986","article-title":"Protection against Brucella abortus in mice with O-polysaccharide-specific monoclonal antibodies","volume":"51","author":"Montaraz","year":"1986","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib74","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.2460\/ajvr.1989.50.12.2158","article-title":"Protection of mice against Brucella abortus infection by inoculation with monoclonal antibodies recognizing Brucella O-antigen","volume":"50","author":"Philips","year":"1989","journal-title":"Am J Vet Res"},{"key":"10.1016\/j.ajpath.2015.03.003_bib75","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1128\/IAI.57.11.3438-3444.1989","article-title":"Capacity of passively administered antibody to prevent establishment of Brucella abortus infection in mice","volume":"57","author":"Winter","year":"1989","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib76","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1615\/CritRevImmunol.v26.i5.30","article-title":"Host immune responses to the intracellular bacteria Brucella: does the bacteria instruct the host to facilitate chronic infection?","volume":"26","author":"Baldwin","year":"2006","journal-title":"Crit Rev Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib77","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/IAI.60.4.1465-1472.1992","article-title":"Effect of recombinant human macrophage colony-stimulating factor 1 on immunopathology of experimental brucellosis in mice","volume":"60","author":"Doyle","year":"1992","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib78","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0966-842X(93)90115-8","article-title":"Macrophage control of Brucella abortus: influence of cytokines and iron","volume":"1","author":"Baldwin","year":"1993","journal-title":"Trends Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib79","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1128\/IAI.63.7.2720-2728.1995","article-title":"Human peripheral blood CD4+ and CD8+ T cells express Th1-like cytokine mRNA and proteins following in\u00a0vitro stimulation with heat-inactivated Brucella abortus","volume":"63","author":"Zaitseva","year":"1995","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib80","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1093\/intimm\/5.8.877","article-title":"Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-gamma in CD4+ T cells","volume":"5","author":"Svetic","year":"1993","journal-title":"Int Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib81","doi-asserted-by":"crossref","first-page":"e1003454","DOI":"10.1371\/journal.ppat.1003454","article-title":"CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function","volume":"9","author":"Xavier","year":"2013","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib82","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/IAI.63.1.264-270.1995","article-title":"Comparison of immune responses and resistance to brucellosis in mice vaccinated with Brucella abortus 19 or RB51","volume":"63","author":"Stevens","year":"1995","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib83","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1128\/IAI.62.8.3206-3212.1994","article-title":"Immune and pathologic responses in mice infected with Brucella abortus 19, RB51, or 2308","volume":"62","author":"Stevens","year":"1994","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib84","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1006\/biol.2000.0249","article-title":"In\u00a0vitro markers and biological activity in mice of seed lot strains and commercial Brucella melitensis Rev 1 and Brucella abortus B19 vaccines","volume":"28","author":"Grillo","year":"2000","journal-title":"Biologicals"},{"key":"10.1016\/j.ajpath.2015.03.003_bib85","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1371\/journal.ppat.0040021","article-title":"Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1","volume":"4","author":"Salcedo","year":"2008","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.ajpath.2015.03.003_bib86","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000238662","article-title":"Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis","volume":"35","author":"Colmenero Castillo","year":"1989","journal-title":"Chemotherapy"},{"key":"10.1016\/j.ajpath.2015.03.003_bib87","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1021\/bi300298v","article-title":"Type IV secretion system core component VirB8 from Brucella binds to the globular domain of VirB5 and to a periplasmic domain of VirB6","volume":"51","author":"Villamil Giraldo","year":"2012","journal-title":"Biochemistry"},{"key":"10.1016\/j.ajpath.2015.03.003_bib88","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1128\/IAI.00993-10","article-title":"An in\u00a0vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation","volume":"79","author":"Paschos","year":"2011","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib89","doi-asserted-by":"crossref","first-page":"7252","DOI":"10.1073\/pnas.0600862103","article-title":"Dimerization and interactions of Brucella suis VirB8 with VirB4 and VirB10 are required for its biological activity","volume":"103","author":"Paschos","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ajpath.2015.03.003_bib90","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.chembiol.2012.07.007","article-title":"Identification of the binding site of Brucella VirB8 interaction inhibitors","volume":"19","author":"Smith","year":"2012","journal-title":"Chem Biol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib91","doi-asserted-by":"crossref","first-page":"743509","DOI":"10.1155\/2013\/743509","article-title":"A history of the development of Brucella vaccines","volume":"2013","author":"Avila-Calderon","year":"2013","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.ajpath.2015.03.003_bib92","first-page":"667","article-title":"Studies of vaccination during calfhood to prevent bovine infectious abortion","volume":"41","author":"Buck","year":"1930","journal-title":"J Agric Res"},{"key":"10.1016\/j.ajpath.2015.03.003_bib93","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0021-9975(67)90038-2","article-title":"Rev. 1 Brucella melitensis vaccine. The stability of the degree of attenuation","volume":"77","author":"Alton","year":"1967","journal-title":"J Comp Pathol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib94","first-page":"409","article-title":"Immunization with viable Brucella organisms. Results of a safety test in humans","volume":"26","author":"Spink","year":"1962","journal-title":"Bull World Health Organ"},{"key":"10.1016\/j.ajpath.2015.03.003_bib95","first-page":"291","article-title":"Efficacy and safety of abortion vaccines prepared from Brucella abortus strains of different degrees of virulence","volume":"46","author":"Cotton","year":"1933","journal-title":"J Agric Res"},{"key":"10.1016\/j.ajpath.2015.03.003_bib96","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0378-1135(91)90091-S","article-title":"Biological properties of RB51; a stable rough strain of Brucella abortus","volume":"28","author":"Schurig","year":"1991","journal-title":"Vet Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib97","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1128\/JB.73.2.211-217.1957","article-title":"Immunization against Brucella infection. VI. Immunity conferred on goats by a nondependent mutant from a streptomycin-dependent mutant strain of Brucella melitensis","volume":"73","author":"Elberg","year":"1957","journal-title":"J Bacteriol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib98","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1128\/IAI.05330-11","article-title":"Protective efficacy and safety of Brucella melitensis 16MDeltamucR against intraperitoneal and aerosol challenge in BALB\/c mice","volume":"79","author":"Arenas-Gamboa","year":"2011","journal-title":"Infect Immun"},{"key":"10.1016\/j.ajpath.2015.03.003_bib99","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1471-2180-6-102","article-title":"Mariner mutagenesis of Brucella melitensis reveals genes with previously uncharacterized roles in virulence and survival","volume":"6","author":"Wu","year":"2006","journal-title":"BMC Microbiol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib100","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/ni.1857","article-title":"TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages","volume":"11","author":"Martinon","year":"2010","journal-title":"Nat Immunol"},{"key":"10.1016\/j.ajpath.2015.03.003_bib101","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrmicro3393","article-title":"Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes?","volume":"13","author":"Celli","year":"2015","journal-title":"Nat Rev Microbiol"}],"container-title":["The American Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944015001832?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002944015001832?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T14:23:54Z","timestamp":1747923834000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002944015001832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6]]},"references-count":101,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["S0002944015001832"],"URL":"https:\/\/doi.org\/10.1016\/j.ajpath.2015.03.003","relation":{},"ISSN":["0002-9440"],"issn-type":[{"value":"0002-9440","type":"print"}],"subject":[],"published":{"date-parts":[[2015,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathogenesis and Immunobiology of Brucellosis","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajpath.2015.03.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}