This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Delpino, M. V.
Right arrow Articles by Baldi, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delpino, M. V.
Right arrow Articles by Baldi, P. C.

 Previous Article  |  Next Article 

Infection and Immunity, March 2009, p. 984-995, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01259-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection with Brucella spp.{triangledown}

M. Victoria Delpino, Carlos A. Fossati, and Pablo C. Baldi*

Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica, UBA, Junín 956, 1113 Buenos Aires, Argentina

Received 14 October 2008/ Returned for modification 27 November 2008/ Accepted 6 December 2008

The ability of Brucella spp. to infect human osteoblasts and the cytokine response of these cells to infection were investigated in vitro. Brucella abortus, B. suis, B. melitensis, and B. canis were able to infect the SaOS-2 and MG-63 osteoblastic cell lines, and the first three species exhibited intracellular replication. B. abortus internalization was not significantly affected by pretreatment of cells with cytochalasin D but was inhibited up to 92% by colchicine. A virB10 mutant of B. abortus could infect but not replicate within osteoblasts, suggesting a role for the type IV secretion system in intracellular survival. Infected osteoblasts produced low levels of chemokines (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did not produce proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor alpha [TNF-{alpha}]). However, osteoblasts stimulated with culture supernatants from Brucella-infected human monocytes (THP-1 cell line) produced chemokines at levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected osteoblasts and also produced IL-6. In the inverse experiment, culture supernatants from Brucella-infected osteoblasts induced the production of IL-8, IL-1β, IL-6, and TNF-{alpha} by THP-1 cells. The induction of TNF-{alpha} and IL-1β was largely due to granulocyte-macrophage colony-stimulating factor produced by infected osteoblasts, as demonstrated by inhibition with a specific neutralizing antibody. This study shows that Brucella can invade and replicate within human osteoblastic cell lines, which can directly and indirectly mount a proinflammatory response. Both phenomena may have a role in the chronic inflammation and bone and joint destruction observed in osteoarticular brucellosis.

* Corresponding author. Mailing address: IDEHU, Facultad de Farmacia y Bioquímica, UBA, Junín 956 4to. Piso, 1113 Buenos Aires, Argentina. Phone: 54-11-4964-8259. Fax: 54-11-4964-0024. E-mail: pablobal{at}ffyb.uba.ar

{triangledown} Published ahead of print on 22 December 2008.

Editor: S. R. Blanke

Infection and Immunity, March 2009, p. 984-995, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01259-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»