Brucella abortus-infected macrophages modulate T lymphocytes to promote osteoclastogenesis via IL-17

GIAMBARTOLOMEI G. H., SCIAN R., ACOSTA- RODRIGUEZ E., FOSSATI C. A., DELPINO M. V.

AMERICAN JOURNAL OF PATHOLOGY

AMER SOC INVESTIGATIVE PATHOLOGY, INC

Lugar: Bethesda ; Año: 2012 vol. 181 p. 887 - 896

0002-9440

The pathogenic mechanisms of bone loss caused by Brucella spp. have not been completely deciphered. Although T lymphocytes are considered important to control infection, the way in which Brucella-induced T cell responses contribute to immunopathology is not know. In this study we present in vitro and in vivo evidence showing that B. abortus-induced inflammatory response leads to the activation of T lymphocytes which further promote osteoclastogenesis. Pre-activated murine T lymphocytes treated with culture supernatant (CS) from macrophages infected with B. abortus induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. 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 since osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMM from IL-17R KO mice. Neutralization experiments indicated that IL-6 generated by Brucella infection induced the production of pro-osteoclastogenic IL-17 from T lymphocytes. Using BMM from TNF receptor (TNFR) p55KO mice it was also demonstrated that IL-17 induced indirectly osteoclastogenesis through the induction of TNF-a from osteoclast precursors. Finally, an extensive and widespread osteoclastogenesis was observed in the knee joints of mice injected with Brucella-activated T cells. Altogether our results indicate activated T cells influenced by the inflammatory milieu elicited by B. abortus-infected macrophages would promote the generation of osteoclasts, leading to bone loss.