{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:01:29Z","timestamp":1792587689608,"version":"4.5.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Brucella<\/jats:italic>\n                    , a major zoonotic pathogen, poses a significant threat to global public health and causes substantial economic losses in the livestock industry. It employs diverse and sophisticated immune evasion strategies to circumvent host surveillance, establishing and maintaining chronic infections that are difficult to treat and prone to relapse. While previous reviews have catalogued individual virulence factors\u2014such as the VirB type IV secretion system\u2014and their actions on pathways like TLR4 signaling, most analyses focus on isolated stages or mechanisms, overlooking the integrated, dynamic regulation spanning the entire infection course. A systematic framework explaining how Brucella modulates host immunity through multi-stage, multidimensional evasion is still lacking. This review synthesizes research from the past decade to delineate the Brucella immune-evasion network across four distinct stages: colonization, latency, acute disease, and chronic persistence. We propose a Spatiotemporal Dynamic Immune Evasion Model that unifies these processes, offering novel insights into the immunological basis of chronic brucellosis and providing a foundation for developing stage-specific therapeutics and next-generation vaccines with strong translational potential.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1707297","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:34:34Z","timestamp":1767854074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatiotemporal dynamics of Brucella immune evasion across infection stages"],"prefix":"10.3389","volume":"16","author":[{"given":"Yu","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Sa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanbing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2295398","DOI":"10.1080\/07853890.2023.2295398","article-title":"Brucellosis: epidemiology, pathogenesis, diagnosis and treatment-a comprehensive review","volume":"55","author":"Qureshi","year":"2024","journal-title":"Ann Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2909.230052","article-title":"Global estimate of human brucellosis incidence","volume":"29","author":"Laine","year":"2023","journal-title":"Emerg Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"122986","DOI":"10.1016\/j.lfs.2024.122986","article-title":"The development of a human Brucella mucosal vaccine: What should be considered","volume":"355","author":"Tian","year":"2024","journal-title":"Life Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010635","article-title":"Antibiotic persistence of intracellular Brucella abortus","volume":"16","author":"Mode","year":"2022","journal-title":"PloS Negl Trop Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.21307\/pjm-2018-029","article-title":"Brucella - virulence factors, pathogenesis and treatment","volume":"67","author":"G\u0142owacka","year":"2018","journal-title":"Pol J Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1608617","article-title":"Beyond survival to domination: Brucella\u2019s multilayered strategies for evading host immune responses","volume":"16","author":"Wei","year":"2025","journal-title":"Front Microbiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"128015","DOI":"10.1016\/j.micres.2024.128015","article-title":"A novel Brucella T4SS effector RS15060 acts on bacterial morphology, lipopolysaccharide core synthesis and host proinflammatory responses, which is beneficial for Brucella melitensis virulence","volume":"292","author":"Yin","year":"2024","journal-title":"Microbiol Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1352306","article-title":"Brucella abortus triggers the differential expression of immunomodulatory lncRNAs in infected murine macrophages","volume":"15","author":"Flores-Concha","year":"2024","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.702881","article-title":"Brucella spp. Omp25 Promotes Proteasome-Mediated cGAS Degradation to Attenuate IFN-\u03b2 Production","volume":"12","author":"Li","year":"2021","journal-title":"Front Microbiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1408407","article-title":"Brucella mediates autophagy, inflammation, and apoptosis to escape host killing","volume":"14","author":"Qin","year":"2024","journal-title":"Front Cell Infect Microbiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.3390\/ijms22073673","article-title":"The mechanism of facultative intracellular parasitism of brucella","volume":"22","author":"Jiao","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.3390\/microorganisms10071260","article-title":"Immunosuppressive mechanisms in brucellosis in light of chronic bacterial diseases","volume":"10","author":"Pellegrini","year":"2022","journal-title":"Microorganisms"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1342684","article-title":"Brucella infection and Toll-like receptors","volume":"14","author":"Yu","year":"2024","journal-title":"Front Cell Infect Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00178","article-title":"The role of the flagellar protein flgJ in the virulence of brucella abortus","volume":"10","author":"Coloma-Rivero","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.3390\/microorganisms10102003","article-title":"Brucella phagocytosis mediated by pathogen-host interactions and their intracellular survival","volume":"10","author":"Huy","year":"2022","journal-title":"Microorganisms"},{"key":"B16","doi-asserted-by":"publisher","first-page":"105026","DOI":"10.1016\/j.actatropica.2019.05.017","article-title":"Screening and identification of a human domain antibody against Brucella abortus VirB5","volume":"197","author":"Deng","year":"2019","journal-title":"Acta Trop"},{"key":"B17","doi-asserted-by":"publisher","first-page":"105930","DOI":"10.1016\/j.micpath.2022.105930","article-title":"Development and evaluation of the Galleria mellonella (greater wax moth) infection model to study Brucella host-pathogen interaction","volume":"174","author":"Elizalde-Bielsa","year":"2022","journal-title":"Microb Pathog"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00629.x","article-title":"Differential inductions of TNF-alpha and IGTP, IIGP by structurally diverse classic and non-classic lipopolysaccharides","volume":"8","author":"Lapaque","year":"2006","journal-title":"Cell Microbiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.3390\/ijms22073673","article-title":"The mechanism of facultative intracellular parasitism of brucella","volume":"22","author":"Jiao","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102905","article-title":"Interactions of the human pathogenic Brucella species with their hosts","volume":"65","author":"Atluri","year":"2011","journal-title":"Annu Rev Microbiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502040102","article-title":"Evasion of Toll-like receptor 5 by flagellated bacteria","volume":"102","author":"Andersen-Nissen","year":"2005","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2005.02622.x","article-title":"Brucellosis\u2013new aspects of an old disease","volume":"98","author":"Cutler","year":"2005","journal-title":"J Appl Microbiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2429-2433.2004","article-title":"Different responses of macrophages to smooth and rough Brucella spp.: relationship to virulence","volume":"72","author":"Jim\u00e9nez de Bag\u00fc\u00e9s","year":"2004","journal-title":"Infect Immun"},{"key":"B24","doi-asserted-by":"publisher","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":"B25","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1640-1644.2002","article-title":"Role of cholesterol and the ganglioside GM(1) in entry and short-term survival of Brucella suis in murine macrophages","volume":"70","author":"Naroeni","year":"2002","journal-title":"Infect Immun"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12223-019-00691-6","article-title":"Dendritic cells and Brucella spp. interaction: the sentinel host and the stealthy pathogen","volume":"65","author":"Avila-Calder\u00f3n","year":"2019","journal-title":"Folia Microbiol (Praha)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1462399407000543","article-title":"Virulence factors in brucellosis: implications for aetiopathogenesis and treatment","volume":"9","author":"Fugier","year":"2007","journal-title":"Expert Rev Mol Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1129172","article-title":"The mechanism of chronic intracellular infection with Brucella spp","volume":"13","author":"Guo","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00982.x","article-title":"An evolutionary strategy for a stealthy intracellular Brucella pathogen","volume":"240","author":"Martirosyan","year":"2011","journal-title":"Immunol Rev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.08.134","article-title":"The UTP-glucose-1-phosphate uridylyltransferase of Brucella melitensis inhibits the activation of NF-\u03baB via regulating the bacterial type IV secretion system","volume":"164","author":"Zhou","year":"2020","journal-title":"Int J Biol Macromol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-019-01651-6","article-title":"Deletion of the type IV secretion system effector vceA promotes autophagy and inhibits apoptosis in brucella-infected human trophoblast cells","volume":"76","author":"Zhang","year":"2019","journal-title":"Curr Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.2387-2392.1998","article-title":"Virulent Brucella abortus prevents lysosome fusion and is distributed within autophagosome-like compartments","volume":"66","author":"Pizarro-Cerd\u00e1","year":"1998","journal-title":"Infect Immun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030088","article-title":"Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum","volume":"198","author":"Celli","year":"2003","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1621230","article-title":"Brucellosis: Bacteriology, pathogenesis, epidemiology and role of the metallophores in virulence: a review","volume":"15","author":"Ghssein","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1408407","article-title":"Brucella mediates autophagy, inflammation, and apoptosis to escape host killing","volume":"14","author":"Qin","year":"2024","journal-title":"Front Cell Infect Microbiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00718.x","article-title":"Brucella intracellular replication requires trafficking through the late endosomal\/lysosomal compartment","volume":"9","author":"Starr","year":"2008","journal-title":"Traffic"},{"key":"B37","doi-asserted-by":"publisher","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":"B38","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1471-2180-9-92","article-title":"DNA polymorphism analysis of Brucella lipopolysaccharide genes reveals marked differences in O-polysaccharide biosynthetic genes between smooth and rough Brucella species and novel species-specific markers","volume":"9","author":"Zygmunt","year":"2009","journal-title":"BMC Microbiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13567-017-0422-9","article-title":"Characterization of Brucella abortus mutant strain \u039422915, a potential vaccine candidate","volume":"48","author":"Bao","year":"2017","journal-title":"Vet Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"109699","DOI":"10.1016\/j.vetmic.2023.109699","article-title":"Effect of ubiquitin-proteasome system and autophagy-lysosome pathway on intracellular replication of Brucella.suis","volume":"280","author":"Dong","year":"2023","journal-title":"Vet Microbiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.603457","article-title":"Global lysine crotonylation alterations of host cell proteins caused by brucella effector bspF","volume":"10","author":"Zhu","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/s41467-024-55799-2","article-title":"Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils","volume":"16","author":"Pellegrini","year":"2025","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011672","article-title":"Interactions between B cells and T follicular regulatory cells enhance susceptibility to Brucella infection independent of the anti-Brucella humoral response","volume":"19","author":"Dadelahi","year":"2023","journal-title":"PloS Pathog"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.702881","article-title":"Brucella spp. Omp25 Promotes Proteasome-Mediated cGAS Degradation to Attenuate IFN-\u03b2 Production","volume":"12","author":"Li","year":"2021","journal-title":"Front Microbiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00281-18","article-title":"Brucella peptide cross-reactive major histocompatibility complex class I presentation activates SIINFEKL-specific T cell receptor-expressing T cells","volume":"86","author":"Harms","year":"2018","journal-title":"Infect Immun"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0306429","article-title":"Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-\u03b3-induced MHC-I expression in epithelial and endothelial cells","volume":"19","author":"Serafino","year":"2024","journal-title":"PloS One"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.111","article-title":"Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway","volume":"95","author":"Vel\u00e1squez","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"15123","DOI":"10.1038\/s41598-022-19398-9","article-title":"Expression of NLRP3 and AIM2 inflammasome in Peripheral blood in Chinese patients with acute and chronic brucellosis","volume":"12","author":"Su","year":"2022","journal-title":"Sci Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14422","article-title":"Brucella induces heme oxygenase-1 expression to promote its infection","volume":"69","author":"Hu","year":"2021","journal-title":"Transbound Emerg Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.5.913","article-title":"Isolation of components of Brucella abortus responsible for inhibition of function in bovine neutrophils","volume":"152","author":"Canning","year":"1985","journal-title":"J Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.micpath.2008.10.011","article-title":"The IFNgamma-induced STAT1-CBP\/P300 association, required for a normal response to the cytokine, is disrupted in Brucella-infected macrophages","volume":"46","author":"Bouhet","year":"2008","journal-title":"Microb Pathog"},{"key":"B52","doi-asserted-by":"publisher","first-page":"31876","DOI":"10.1038\/srep31876","article-title":"The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis","volume":"6","author":"Wang","year":"2016","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.22099\/ijvr.2024.48969.7177","article-title":"Effects of major OMPs and LPS of Brucella on the control of activation of bone marrow-derived dendritic cells and proliferation of T-lymphocytes in mice","volume":"25","author":"Xu","year":"2024","journal-title":"Iran J Vet Res"},{"key":"B54","doi-asserted-by":"publisher","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":"B55","doi-asserted-by":"publisher","first-page":"120020","DOI":"10.1016\/j.carbpol.2022.120020","article-title":"A polysaccharide from native Curcuma kwangsiensis and its mechanism of reversing MDSC-induced suppressive function","volume":"297","author":"Jiang","year":"2022","journal-title":"Carbohydr Polym"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.226","article-title":"Single-cell landscape revealed immune characteristics associated with disease phases in brucellosis patients","volume":"3","author":"Wang","year":"2024","journal-title":"Imeta"},{"key":"B57","doi-asserted-by":"publisher","first-page":"jiaf522","DOI":"10.1093\/infdis\/jiaf522","article-title":"Single-cell transcriptome profiling reveals the immune dysregulation characteristics of mice infected by Brucella abortus","volume":"11","author":"Zhang","year":"2025","journal-title":"J Infect Dis"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1574006","article-title":"Brucella infection induces chromatin restructuring in host cells to activate immune responses","volume":"16","author":"Xie","year":"2025","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1707297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:34:36Z","timestamp":1767854076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1707297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2025.1707297"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1707297","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"article-number":"1707297"}}