Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. In this manuscript, we described an immune mechanism for inflammatory bone loss in response to infection by Brucella abortus . We established a requirement for MyD88 and TLR2 in TNF-α-elicited osteoclastogenesis in response to B. abortus infection. CS from macrophages infected with B. abortus induced BMM to undergo osteoclastogenesis. Although B. abortus -infected macrophages actively secreted IL-1β, IL-6, and TNF-α, osteoclastogenesis depended on TNF-α, as CS from B. abortus -infected macrophages failed to induce osteoclastogenesis in BMM from TNFRp55 –/– mice. CS from B. abortus -stimulated MyD88 –/– and TLR2 –/– macrophages failed to express TNF-α, and these CS induced no osteoclast formation compared with that of the WT or TLR4 –/– macrophages. Omp19, a B. abortus lipoprotein model, recapitulated the cytokine production and subsequent osteoclastogenesis induced by the whole bacterium. All phenomena were corroborated using human monocytes, indicating that this mechanism could play a role in human osteoarticular brucellosis. Our results indicate that B. abortus , through its lipoproteins, may be involved in bone resorption through the pathological induction of osteoclastogenesis. osteoclast bone inflammation bacteria lipoprotein innate immunity Footnotes –/– knockout BMM bone marrow-derived monocyte(s) Ckb cytoplasmic creatine kinase CS culture supernatant(s) HKBA heat-killed Brucella abortus IDEHU Instituto de Estudios de la Inmunidad Humoral (CONICET) KO knockout L-Omp19 lipidated outer membrane protein 19 MOI multiplicities of infection Omp19 outer membrane protein 19 Pam 3 Cys synthetic lipohexapeptide tripalmitoyl-S-glyceryl-Cys-Ser-Lys4-OH TRAP tartrate-resistant acid phosphatase TSA tryptose soy agar U-Omp19 unlipidated outer membrane protein 19 Received April 5, 2011. Revision received September 29, 2011. Accepted October 14, 2011. © 2012 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print November 10, 2011 , doi: 10.1189/jlb.04111185 February 2012 Journal of Leukocyte Biology vol. 91 no. 2 285-298 » Abstract Full Text Full Text (PDF) All Versions of this Article: jlb.04111185v1 91/2/285 most recent Classifications Inflammation, Extracellular Mediators, & Effector Molecules Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Delpino, M. V. Articles by Giambartolomei, G. H. PubMed PubMed citation Articles by Delpino, M. V. Articles by Giambartolomei, G. H. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 91 (2) From the Cover Editorials: Tim-3 puts on the brakes. Editorials: T cell memory, bone marrow, and aging: the good news. Spotlight on Leading Edge Research: Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes. Spotlight on Leading Edge Research: The impact of aging on memory T cell phenotype and function in the human bone marrow. Reviews: Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. Reviews: Non-human primate dendritic cells. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2012 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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