Macrophage-elicited osteoclastogenesis in response to Brucella abortus infection requires TLR2/MyD88-dependent TNF-alpha production

作者：Victoria Delpino M; Barrionuevo Paula; Macedo Gilson Costa; Oliveira Sergio Costa; Di Genaro Silvia; Scian Romina; Cruz Miraglia M; Fossati Carlos A; Baldi Pablo C; Giambartolomei Guillermo H^*

来源：Journal of Leukocyte Biology, 2012, 91(2): 285-298.

DOI：10.1189/jlb.04111185

• osteoclast
• bone
• inflammation
• bacteria
• lipoprotein
• innate immunity

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-alpha-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-1 beta, IL-6, and TNF-alpha, osteoclastogenesis depended on TNF-alpha, 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-alpha, 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. J. Leukoc. Biol. 91: 285-298; 2012.

• 出版日期2012-2