| First Author | Giambartolomei GH | Year | 2012 |
| Journal | Am J Pathol | Volume | 181 |
| Issue | 3 | Pages | 887-96 |
| PubMed ID | 22901753 | Mgi Jnum | J:189928 |
| Mgi Id | MGI:5447256 | Doi | 10.1016/j.ajpath.2012.05.029 |
| Citation | Giambartolomei GH, et al. (2012) Brucella abortus-infected macrophages modulate T lymphocytes to promote osteoclastogenesis via IL-17. Am J Pathol 181(3):887-96 |
| abstractText | The pathogenic mechanisms of bone loss caused by Brucella species have not been completely deciphered. Although T lymphocytes (LTs) are considered important to control infection, the mechanism of Brucella-induced T-cell responses to immunopathological features is not known. We present in vitro and in vivo evidence showing that Brucella abortus-induced inflammatory response leads to the activation of LTs, which further promote osteoclastogenesis. Pre-activated murine LTs treated with culture supernatant from macrophages infected with B. abortus induced bone marrow-derived monocytes (BMMs) to undergo osteoclastogenesis. Furthermore, osteoclastogenesis was mediated by CD4(+) T cells. Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. Neutralization experiments indicated that IL-6, generated by Brucella infection, induced the production of pro-osteoclastogenic IL-17 from LTs. By using BMMs from tumor necrosis factor receptor p55 knockout mice, we also demonstrated that IL-17 indirectly induced osteoclastogenesis through the induction of tumor necrosis factor-alpha from osteoclast precursors. Finally, extensive and widespread osteoclastogenesis was observed in the knee joints of mice injected with Brucella-activated T cells. Our results indicate that activated T cells, elicited by B. abortus-infected macrophages and influenced by the inflammatory milieu, promote the generation of osteoclasts, leading to bone loss. |
