{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:53:02Z","timestamp":1791499982215,"version":"4.3.4"},"reference-count":81,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brucellosis is a highly prevalent zoonotic disease characterized by abortion and reproductive dysfunction in pregnant animals. Although the mortality rate of Brucellosis is low, it is harmful to human health, and also seriously affects the development of animal husbandry, tourism and international trade. Brucellosis is caused by Brucella, which is a facultative intracellular parasitic bacteria. It mainly forms Brucella-containing vacuoles (BCV) in the host cell to avoid the combination with lysosome (Lys), so as to avoid the elimination of it by the host immune system. Brucella not only has the ability to resist the phagocytic bactericidal effect, but also can make the host cells form a microenvironment which is conducive to its survival, reproduction and replication, and survive in the host cells for a long time, which eventually leads to the formation of chronic persistent infection. Brucella can proliferate and replicate in cells, evade host immune response and induce persistent infection, which are difficult problems in the treatment and prevention of Brucellosis. Therefore, the paper provides a preliminary overview of the facultative intracellular parasitic and immune escape mechanisms of Brucella, which provides a theoretical basis for the later study on the pathogenesis of Brucella.<\/jats:p>","DOI":"10.3390\/ijms22073673","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"3673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["The Mechanism of Facultative Intracellular Parasitism of Brucella"],"prefix":"10.3390","volume":"22","author":[{"given":"Hanwei","family":"Jiao","sequence":"first","affiliation":[{"name":"Immunology Research Center, Medical Research Institute, Southwest University, Chongqing 402460, China"},{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"},{"name":"Veterinary Scientific Engineering Research Center, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojing","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1473-3099(06)70382-6","article-title":"The new global map of human Brucellosis","volume":"6","author":"Pappas","year":"2006","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e501","DOI":"10.1097\/MPH.0000000000000849","article-title":"Secondary Hemophagocytic Lymphohistocytosis in a Child with Brucellosis","volume":"39","author":"Pekpak","year":"2017","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_3","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":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.20506\/rst.32.1.2204","article-title":"New developments in the diagnostic procedures for zoonotic Brucellosis in humans","volume":"32","author":"Sprague","year":"2013","journal-title":"Rev. Sci. Tech."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0255-0857(21)02105-8","article-title":"Review of clinical and laboratory features of human Brucellosis","volume":"25","author":"Mantur","year":"2007","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.20506\/rst.32.1.2188","article-title":"Epidemiology of Brucellosis in domestic animals caused by Brucella melitensis, Brucella suis and Brucella abortus","volume":"32","year":"2013","journal-title":"Rev. Sci Tech."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1475-2859-5-13","article-title":"Brucella spp noncanonical LPS: Structure, biosynthesis, and interaction with host immune system","volume":"5","author":"Cardoso","year":"2006","journal-title":"Microb. Cell Fact."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0378-1135(95)00153-0","article-title":"Infection of cattle with Yersinia enterocolitica O:9 a cause of the false positive serological reactions in bovine Brucellosis diagnostic tests","volume":"48","author":"Weynants","year":"1996","journal-title":"Vet. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Copin, R., Vitry, M.A., Hanot Mambres, D., Machelart, A., De Trez, C., Vanderwinden, J.M., Magez, S., Akira, S., Ryffel, B., and Carlier, Y. (2012). In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002575"},{"key":"ref_10","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":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1574-6976.2012.00334.x","article-title":"Internal affairs: Investigating the Brucella intracellular lifestyle","volume":"36","author":"Gorvel","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","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":"ref_13","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":"ref_14","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1111\/j.1365-2672.2005.02622.x","article-title":"Brucellosis--new aspects of an old disease","volume":"98","author":"Cutler","year":"2005","journal-title":"J. Appl. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2429","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":"Terraza","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_16","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":"ref_17","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":"ref_18","doi-asserted-by":"crossref","first-page":"1640","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":"ref_19","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1128\/IAI.71.3.1481-1490.2003","article-title":"Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages","volume":"71","author":"Porte","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"678","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":"ref_21","doi-asserted-by":"crossref","unstructured":"Celli, J. (2019). The Intracellular Life Cycle of Brucella spp.. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.BAI-0006-2019"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0378-1135(02)00214-6","article-title":"Brucella intracellular life: From invasion to intracellular replication","volume":"90","author":"Gorvel","year":"2002","journal-title":"Vet. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"523","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":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev-animal-021815-111326","article-title":"Brucella spp. Virulence Factors and Immunity","volume":"4","author":"Byndloss","year":"2016","journal-title":"Annu Rev. Anim Biosci"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1099\/mic.0.28326-0","article-title":"The putative lytic transglycosylase VirB1 from Brucella suis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11","volume":"151 Pt 11","author":"Hoppner","year":"2005","journal-title":"Microbiology (Reading)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1128\/IAI.72.9.5143-5149.2004","article-title":"Differential requirements for VirB1 and VirB2 during Brucella abortus infection","volume":"72","author":"Sun","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1128\/IAI.71.3.1075-1082.2003","article-title":"Production of the type IV secretion system differs among Brucella species as revealed with VirB5- and VirB8-specific antisera","volume":"71","author":"Rouot","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jmb.2006.04.060","article-title":"A large domain swap in the VirB11 ATPase of Brucella suis leaves the hexameric assembly intact","volume":"360","author":"Hare","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S1995-7645(12)60089-3","article-title":"Molecular cloning of virB12 gene of Brucella melitensis 16M strain in pET28a vector","volume":"5","author":"Mirkalantari","year":"2012","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fcimb.2015.00072","article-title":"Type IV secretion system of Brucella spp. and its effectors","volume":"5","author":"Ke","year":"2015","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/infdis\/jiq163","article-title":"The virB operon is essential for lethality of Brucella microti in the Balb\/c murine model of infection","volume":"203","author":"Hanna","year":"2011","journal-title":"J. Infect. Dis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1128\/IAI.67.8.4041-4047.1999","article-title":"Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages","volume":"67","author":"Porte","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00430-009-0123-8","article-title":"Survival of the fittest: How Brucella strains adapt to their intracellular niche in the host","volume":"198","author":"Roop","year":"2009","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/infdis\/jiu673","article-title":"Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain","volume":"211","author":"Keriel","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zygmunt, M.S., Blasco, J.M., Letesson, J.J., Cloeckaert, A., and Moriyon, I. (2009). 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. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-92"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.21307\/pjm-2018-029","article-title":"Brucella\u2014Virulence Factors, Pathogenesis and Treatment","volume":"67","author":"Glowacka","year":"2018","journal-title":"Pol. J. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/21505594.2017.1386831","article-title":"Immunomodulatory properties of Brucella melitensis lipopolysaccharide determinants on mouse dendritic cells in vitro and in vivo","volume":"9","author":"Zhao","year":"2018","journal-title":"Virulence"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5238","DOI":"10.1128\/IAI.71.9.5238-5244.2003","article-title":"Purification and characterization of an immunogenic aminopeptidase of Brucella melitensis","volume":"71","author":"Contreras","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.micro.57.030502.090803","article-title":"Brucella stationary-phase gene expression and virulence","volume":"57","author":"Roop","year":"2003","journal-title":"Annu Rev. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.1128\/IAI.73.12.8353-8361.2005","article-title":"Whole-genome analyses of speciation events in pathogenic Brucellae","volume":"73","author":"Chain","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1128\/IAI.71.5.2927-2932.2003","article-title":"Production of the siderophore 2,3-dihydroxybenzoic acid is required for wild-type growth of Brucella abortus in the presence of erythritol under low-iron conditions in vitro","volume":"71","author":"Bellaire","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.4014\/jmb.1805.05068","article-title":"Genes Related to Intracellular Survival of Brucella abortus in THP-1 Macrophage Cells","volume":"28","author":"Shim","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_43","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":"ref_44","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/nature07830","article-title":"The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex","volume":"458","author":"Park","year":"2009","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"401","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":"ref_46","doi-asserted-by":"crossref","first-page":"9247","DOI":"10.1073\/pnas.0502040102","article-title":"Evasion of Toll-like receptor 5 by flagellated bacteria","volume":"102","author":"Smith","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.1128\/jb.178.20.5867-5876.1996","article-title":"Brucella-Salmonella lipopolysaccharide chimeras are less permeable to hydrophobic probes and more sensitive to cationic peptides and EDTA than are their native Brucella spp. counterparts","volume":"178","author":"Freer","year":"1996","journal-title":"J. Bacteriol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Barquero-Calvo, E., Mora-Cartin, R., Arce-Gorvel, V., de Diego, J.L., Chacon-Diaz, C., Chaves-Olarte, E., Guzman-Verri, C., Buret, A.G., Gorvel, J.P., and Moreno, E. (2015). Brucella abortus Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004853"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mora-Cartin, R., Gutierrez-Jimenez, C., Alfaro-Alarcon, A., Chaves-Olarte, E., Chacon-Diaz, C., Barquero-Calvo, E., and Moreno, E. (2019). Neutrophils Dampen Adaptive Immunity in Brucellosis. Infect. Immun., 87.","DOI":"10.1128\/IAI.00118-19"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/1753425910367526","article-title":"Regulatory role of natural killer (NK) cells on antibody responses to Brucella abortus","volume":"17","author":"Gao","year":"2011","journal-title":"Innate Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.micinf.2010.10.020","article-title":"Brucella abortus inhibits IFN-gamma-induced FcgammaRI expression and FcgammaRI-restricted phagocytosis via toll-like receptor 2 on human monocytes\/macrophages","volume":"13","author":"Barrionuevo","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"388","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":"Velasquez","year":"2017","journal-title":"Immunol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","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":"Sharon","year":"2020","journal-title":"Folia Microbiol. (Praha)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2012.00001","article-title":"Antigen-specific acquired immunity in human Brucellosis: Implications for diagnosis, prognosis, and vaccine development","volume":"2","author":"Cannella","year":"2012","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.micinf.2009.09.005","article-title":"CD4+CD25+ T regulatory cells limit effector T cells and favor the progression of Brucellosis in BALB\/c mice","volume":"12","author":"Pasquali","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Spera, J.M., Guaimas, F., Corvi, M.M., and Ugalde, J.E. (2018). Brucella Hijacks Host-Mediated Palmitoylation To Stabilize and Localize PrpA to the Plasma Membrane. Infect. Immun., 86.","DOI":"10.1128\/IAI.00402-18"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.micpath.2014.01.003","article-title":"Brucella alters the immune response in a prpA-dependent manner","volume":"67\u201368","author":"Spera","year":"2014","journal-title":"Microb. Pathog."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00430-014-0356-z","article-title":"Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice","volume":"204","author":"Kianmehr","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Salcedo, S.P., Marchesini, M.I., Lelouard, H., Fugier, E., Jolly, G., Balor, S., Muller, A., Lapaque, N., Demaria, O., and Alexopoulou, L. (2008). Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog, 4.","DOI":"10.1371\/journal.ppat.0040021"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.bbrc.2016.06.064","article-title":"Brucella TIR-like protein TcpB\/Btp1 specifically targets the host adaptor protein MAL\/TIRAP to promote infection","volume":"477","author":"Li","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","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":"Koelblen","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1074\/jbc.M113.523407","article-title":"Crystal structures of the Toll\/Interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry","volume":"289","author":"Snyder","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Durward, M., Radhakrishnan, G., Harms, J., Bareiss, C., Magnani, D., and Splitter, G.A. (2012). Active evasion of CTL mediated killing and low quality responding CD8+ T cells contribute to persistence of Brucellosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034925"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.3389\/fimmu.2019.01759","article-title":"Immune Response to Mucosal Brucella Infection","volume":"10","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/j.1462-5822.2010.01498.x","article-title":"Innate immune encounters of the (Type) 4th kind: Brucella","volume":"12","author":"Rolan","year":"2010","journal-title":"Cell Microbiol."},{"key":"ref_66","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":"ref_67","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1574891X11308010004","article-title":"Microbiology of Brucella","volume":"8","author":"Percin","year":"2013","journal-title":"Recent Pat. Antiinfect. Drug Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1080\/1040841X.2017.1332002","article-title":"Brucella central carbon metabolism: An update","volume":"44","author":"Barbier","year":"2018","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1462-5822.2005.00502.x","article-title":"The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection","volume":"7","author":"Fretin","year":"2005","journal-title":"Cell Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.micinf.2018.12.004","article-title":"Inhibition of antigen presentation by Brucella: Many more than many ways","volume":"21","author":"Barrionuevo","year":"2019","journal-title":"Microbes. Infect."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ni.3306","article-title":"Molecular control of activation and priming in macrophages","volume":"17","author":"Glass","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1189\/jlb.04111185","article-title":"Macrophage-elicited osteoclastogenesis in response to Brucella abortus infection requires TLR2\/MyD88-dependent TNF-alpha production","volume":"91","author":"Delpino","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1574-695X.1996.tb00060.x","article-title":"Endogenous gamma interferon and interleukin-10 in Brucella abortus 2308 infection in mice","volume":"15","author":"Monte","year":"1996","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_74","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":"ref_75","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1128\/iai.63.3.1130-1133.1995","article-title":"Interleukin-10 downregulates protective immunity to Brucella abortus","volume":"63","author":"Fernandes","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Xavier, M.N., Winter, M.G., Spees, A.M., Nguyen, K., Atluri, V.L., Silva, T.M., Baumler, A.J., Muller, W., Santos, R.L., and Tsolis, R.M. (2013). CD4+ T cell-derived IL-10 promotes Brucella abortus persistence via modulation of macrophage function. PLoS Pathog, 9.","DOI":"10.1371\/journal.ppat.1003454"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16514","DOI":"10.1073\/pnas.0603362103","article-title":"A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection","volume":"103","author":"Spera","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1099\/mic.0.27782-0","article-title":"Roles of Brucella abortus SpoT in morphological differentiation and intramacrophagic replication","volume":"151","author":"Kim","year":"2005","journal-title":"Microbiology (Reading)"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1093\/infdis\/jit007","article-title":"Pathogenic Brucella replicate in human trophoblasts","volume":"207","author":"Salcedo","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/030098588602300301","article-title":"Pathogenesis of placentitis in the goat inoculated with Brucella abortus. I. Gross and histologic lesions","volume":"23","author":"Anderson","year":"1986","journal-title":"Vet. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1177\/030098588902600609","article-title":"Intracellular localization of Brucella abortus in bovine placenta","volume":"26","author":"Meador","year":"1989","journal-title":"Vet. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3673\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:25Z","timestamp":1760362405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":81,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073673"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073673","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]}}}