{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:39:36Z","timestamp":1791095976411,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here, we show that<jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>invades and replicates in murine AM without inducing cytotoxicity.<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>infection induced a statistically significant increase of tumor necrosis factor alpha (TNF-\u03b1), CXCL1 or keratinocyte chemoattractant (KC), interleukin-1\u03b2 (IL-1\u03b2), IL-6, and IL-12 in AM from C57BL\/6 mice and BALB\/c mice, but these responses were generally weaker and\/or delayed compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4, and TLR9 revealed that TNF-\u03b1 and KC responses were mediated by TLR2 recognition.<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>infection reduced in a multiplicity of infection-dependent manner the expression of major histocompatibility complex class II (MHC-II) molecules induced by gamma interferon (IFN-\u03b3) in AM. The same phenomenon was induced by incubation with heat-killed<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>(HKBA) or the lipidated form of the 19-kDa outer membrane protein of<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>(L-Omp19), and it was shown to be mediated by TLR2 recognition. In contrast, no significant downregulation of MHC-II was induced by either unlipidated Omp19 or<jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intratracheal infection, viable<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>was detected in AM from both wild-type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>survives in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival.<\/jats:p>","DOI":"10.1128\/iai.01237-13","type":"journal-article","created":{"date-parts":[[2013,11,26]],"date-time":"2013-11-26T04:25:37Z","timestamp":1385439937000},"page":"626-639","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Key Role of Toll-Like Receptor 2 in the Inflammatory Response and Major Histocompatibility Complex Class II Downregulation in Brucella abortus-Infected Alveolar Macrophages"],"prefix":"10.1128","volume":"82","author":[{"given":"Mariana C.","family":"Ferrero","sequence":"first","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (CONICET\/UBA), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Soledad","family":"Hielpos","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (CONICET\/UBA), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia B.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (CONICET\/UBA), Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn,\u201d Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia P.","family":"Corsetti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo H.","family":"Giambartolomei","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (CONICET\/UBA), Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn,\u201d Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo C.","family":"Baldi","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (CONICET\/UBA), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6311-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70382-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1980.tb18912.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.77.3.335"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-8244(97)00098-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1108.041197"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.07.005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.05.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2009.01.010"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040497"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00451-07"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.11.4838-4841.1996"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.07.010"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2005.10.002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-009-0123-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00949-07"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/149.6.942"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.10.6981"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8432"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.4.545"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002099"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02200-10"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00187.2010"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2004.03.007"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.70.2.163","article-title":"Functional heterogeneity in liver and lung macrophages","volume":"70","author":"Laskin DL","year":"2001","unstructured":"LaskinDLWeinbergerBLaskinJD. 2001. Functional heterogeneity in liver and lung macrophages. J. Leukoc. Biol. 70:163\u2013170.","journal-title":"J. Leukoc. Biol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901089"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.7.4635"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.6.3210-3218.2000"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2101-2110.2004"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.2.371"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00164"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.04.031"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2008.07.002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.10.020"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.4049\/jimmunol.163.3.1188","article-title":"CpG oligodeoxynucleotides down-regulate macrophage class II MHC antigen processing","volume":"163","author":"Chu RS","year":"1999","unstructured":"ChuRSAskewDNossEHTobianAKriegAMHardingCV. 1999. CpG oligodeoxynucleotides down-regulate macrophage class II MHC antigen processing. J. Immunol. 163:1188\u20131194.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2321"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.176-186.2004"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.04111185"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-48-12-1065"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.4.1309-1316.1998"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.1080"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.720-723.1995"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2004.65.644"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.017285-0"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3181\/0904-RM-124"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090503"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.7.2782-2786.1996"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.07.004"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.5137-5143.2005"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.05.022"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4487-4497.2003"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5508.1544"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6603-6614.2004"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01237-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01237-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T11:18:26Z","timestamp":1688815106000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01237-13"}},"subtitle":[],"editor":[{"given":"A.","family":"Camilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1128\/IAI.01237-13"],"URL":"https:\/\/doi.org\/10.1128\/iai.01237-13","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2]]},"assertion":[{"value":"2013-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}