{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:57:33Z","timestamp":1791205053193,"version":"4.1.0"},"reference-count":94,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88\/IL-12p35 signaling pathways, or an activation-induced deaminase\u2013mediated isotype switch. In striking contrast, the presence of memory IFN-\u03b3\u2013producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88\/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302561","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T05:23:45Z","timestamp":1395293025000},"page":"3740-3752","source":"Crossref","is-referenced-by-count":74,"title":["Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with <i>Brucella melitensis<\/i>"],"prefix":"10.1093","volume":"192","author":[{"given":"Marie-Alice","family":"Vitry","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche en Biologie des Microorganismes, Laboratoire d\u2019Immunologie et de Microbiologie, Institut Namurois des Sciences de la Vie, Universit\u00e9 de Namur , 5000 Namur,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Hanot Mambres","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Biologie des Microorganismes, Laboratoire d\u2019Immunologie et de Microbiologie, Institut Namurois des Sciences de la Vie, Universit\u00e9 de Namur , 5000 Namur,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"De Trez","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Flanders Institute for Biotechnology, Department of Structural Biology, Free University of Brussels , 1050 Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka 565-0871,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Ryffel","sequence":"additional","affiliation":[{"name":"INSERM, Unit\u00e9 Mixte de Recherche 7355, Immunologie Mol\u00e9culaire, Institut de Transg\u00e9nose, Universit\u00e9 d\u2019Orl\u00e9ans et Centre National de la Recherche Scientifique , 45071 Orleans,","place":["France"]},{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Rondebosch 7701, Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Letesson","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Biologie des Microorganismes, Laboratoire d\u2019Immunologie et de Microbiologie, Institut Namurois des Sciences de la Vie, Universit\u00e9 de Namur , 5000 Namur,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Muraille","sequence":"additional","affiliation":[{"name":"Laboratoire de Parasitologie, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Libre de Bruxelles , 1070 Brussels,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,15]]},"reference":[{"key":"2025032404225521400_r1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/030098588602300301","article-title":"Pathogenesis of placentitis in the goat inoculated with Brucella abortus. 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Immunol."},{"key":"2025032404225521400_r22","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. 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Immunol."},{"key":"2025032404225521400_r26","doi-asserted-by":"crossref","first-page":"e1000703","DOI":"10.1371\/journal.ppat.1000703","article-title":"Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice","volume":"5","author":"Lin","year":"2009","journal-title":"PLoS Pathog."},{"key":"2025032404225521400_r27","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s004360050416","article-title":"Major histocompatibility complex class I- and II-deficient knock-out mice are resistant to primary but susceptible to secondary Eimeria papillata infections","volume":"84","author":"Schito","year":"1998","journal-title":"Parasitol. Res."},{"key":"2025032404225521400_r28","doi-asserted-by":"crossref","first-page":"12713","DOI":"10.1128\/JVI.01675-10","article-title":"MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection","volume":"84","author":"Seo","year":"2010","journal-title":"J. Virol."},{"key":"2025032404225521400_r29","doi-asserted-by":"crossref","first-page":"e1000966","DOI":"10.1371\/journal.ppat.1000966","article-title":"Role of PKR and Type I IFNs in viral control during primary and secondary infection","volume":"6","author":"Nakayama","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032404225521400_r30","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":"2025032404225521400_r31","first-page":"458","article-title":"Cytokine production in the murine response to brucella infection or immunization with antigenic extracts","volume":"80","author":"Zhan","year":"1993","journal-title":"Immunology"},{"key":"2025032404225521400_r32","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1128\/IAI.67.12.6257-6263.1999","article-title":"Induction and regulation of Th1-inducing cytokines by bacterial DNA, lipopolysaccharide, and heat-inactivated bacteria","volume":"67","author":"Huang","year":"1999","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r33","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.4049\/jimmunol.175.6.3964","article-title":"Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9","volume":"175","author":"Huang","year":"2005","journal-title":"J. Immunol."},{"key":"2025032404225521400_r34","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.4049\/jimmunol.171.3.1441","article-title":"Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent","volume":"171","author":"Huang","year":"2003","journal-title":"J. Immunol."},{"key":"2025032404225521400_r35","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.4049\/jimmunol.167.3.1423","article-title":"IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and regulation by IL-10","volume":"167","author":"Huang","year":"2001","journal-title":"J. Immunol."},{"key":"2025032404225521400_r36","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":"2025032404225521400_r37","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1128\/iai.58.1.254-256.1990","article-title":"Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum","volume":"58","author":"Araya","year":"1990","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1297-9716-43-29","article-title":"What have we learned from brucellosis in the mouse model?","volume":"43","author":"Grill\u00f3","year":"2012","journal-title":"Vet. Res."},{"key":"2025032404225521400_r39","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1074-7613(00)80086-2","article-title":"Unresponsiveness of MyD88-deficient mice to endotoxin","volume":"11","author":"Kawai","year":"1999","journal-title":"Immunity"},{"key":"2025032404225521400_r40","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/eji.1830260722","article-title":"Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response","volume":"26","author":"Mattner","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2025032404225521400_r41","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(00)00078-7","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme","volume":"102","author":"Muramatsu","year":"2000","journal-title":"Cell"},{"key":"2025032404225521400_r42","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/0092-8674(91)90448-8","article-title":"Mice lacking MHC class II molecules","volume":"66","author":"Cosgrove","year":"1991","journal-title":"Cell"},{"key":"2025032404225521400_r43","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"2025032404225521400_r44","doi-asserted-by":"crossref","first-page":"6180","DOI":"10.4049\/jimmunol.161.11.6180","article-title":"Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis","volume":"161","author":"Stamm","year":"1998","journal-title":"J. Immunol."},{"key":"2025032404225521400_r45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/350423a0","article-title":"A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene","volume":"350","author":"Kitamura","year":"1991","journal-title":"Nature"},{"key":"2025032404225521400_r46","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.4049\/jimmunol.178.8.5182","article-title":"MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection","volume":"178","author":"Copin","year":"2007","journal-title":"J. Immunol."},{"key":"2025032404225521400_r47","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/nbt1037","article-title":"Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein","volume":"22","author":"Shaner","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"2025032404225521400_r48","doi-asserted-by":"crossref","first-page":"6695","DOI":"10.1128\/IAI.67.12.6695-6697.1999","article-title":"Constitutive and inducible expression of green fluorescent protein in Brucella suis","volume":"67","author":"K\u00f6hler","year":"1999","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r49","doi-asserted-by":"crossref","first-page":"e1002575","DOI":"10.1371\/journal.ppat.1002575","article-title":"In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice","volume":"8","author":"Copin","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025032404225521400_r50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellimm.2006.10.003","article-title":"Treatment of Brucella-susceptible mice with IL-12 increases primary and secondary immunity","volume":"243","author":"Sathiyaseelan","year":"2006","journal-title":"Cell. Immunol."},{"key":"2025032404225521400_r51","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1128\/AAC.37.11.2333","article-title":"Therapy of experimental murine brucellosis with streptomycin alone and in combination with ciprofloxacin, doxycycline, and rifampin","volume":"37","author":"Lang","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"2025032404225521400_r52","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1574-695X.1996.tb00136.x","article-title":"Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308","volume":"16","author":"Fernandes","year":"1996","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"2025032404225521400_r53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0378-1135(02)00222-5","article-title":"Fundamentals of host immune response against Brucella abortus: what the mouse model has revealed about control of infection","volume":"90","author":"Baldwin","year":"2002","journal-title":"Vet. Microbiol."},{"key":"2025032404225521400_r54","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1128\/iai.63.2.720-723.1995","article-title":"Differential induction of macrophage-derived cytokines by live and dead intracellular bacteria in vitro","volume":"63","author":"Zhan","year":"1995","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r55","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1128\/IAI.00761-12","article-title":"Crucial role of gamma interferon-producing CD4+ Th1 cells but dispensable function of CD8+ T cell, B cell, Th2, and Th17 responses in the control of Brucella melitensis infection in mice","volume":"80","author":"Vitry","year":"2012","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r56","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/infdis\/jiq171","article-title":"B cell-deficient mice display markedly enhanced resistance to the intracellular bacterium Brucella abortus","volume":"203","author":"Goenka","year":"2011","journal-title":"J. Infect. Dis."},{"key":"2025032404225521400_r57","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1046\/j.1365-2567.2001.01258.x","article-title":"Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL\/6 and susceptible BALB\/c mice","volume":"103","author":"Murphy","year":"2001","journal-title":"Immunology"},{"key":"2025032404225521400_r58","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1128\/iai.60.10.4407-4409.1992","article-title":"Effects of gamma interferon and indomethacin in preventing Brucella abortus infections in mice","volume":"60","author":"Stevens","year":"1992","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r59","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1128\/iai.61.11.4899-4901.1993","article-title":"Endogenous gamma interferon mediates resistance to Brucella abortus infection","volume":"61","author":"Zhan","year":"1993","journal-title":"Infect. 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Microbiol."},{"key":"2025032404225521400_r63","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/clinids\/20.5.1241","article-title":"Characteristics of and risk factors for relapse of brucellosis in humans","volume":"20","author":"Ariza","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"2025032404225521400_r64","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1574-6976.2010.00211.x","article-title":"Towards a Brucella vaccine for humans","volume":"34","author":"Perkins","year":"2010","journal-title":"FEMS Microbiol. 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Immunol."},{"key":"2025032404225521400_r80","doi-asserted-by":"crossref","first-page":"5502","DOI":"10.1128\/IAI.69.9.5502-5508.2001","article-title":"Induction of specific cytotoxic lymphocytes in mice vaccinated with Brucella abortus RB51","volume":"69","author":"He","year":"2001","journal-title":"Infect. Immun."},{"key":"2025032404225521400_r81","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1128\/IAI.72.4.2081-2087.2004","article-title":"Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells","volume":"72","author":"Mu\u00f1oz-Montesino","year":"2004","journal-title":"Infect. 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