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

DELPINO M. V., BARRIONUEVO P., COSTA MACEDO G., OLIVEIRA S. C., DI GENARO S., SIAN R., MIRAGLIA M. C., FOSSATI C. A., BALDI P. C., GIAMBARTOLOMEI G. H.

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2012 vol. 91 p. 285 - 298

0741-5400

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 tumor necrosis factor-alpha (TNF-a)-elicited osteoclastogenesis in response to B. abortus infection. Culture supernatant (CS) from macrophages infected with B. abortus induced bone marrow-derived macrophages (BMM) to undergo osteoclastogenesis. Although B. abortus-infected macrophages actively secreted interleukin (IL)-6, IL-1b and TNF-a, osteoclastogenesis depended on TNF-a since CS from B. abortus infected macrophages failed to induce osteoclastogenesis in BMM from TNF receptor p55 -/-mice. CS from B. abortus-stimulated MyD88 -/- and TLR2 -/- macrophages failed to express TNF-a, and these CS induced no osteoclast formation compared with that of the wild-type or the TLR4-/- macrophages. Outer membrane protein 19 (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 is involved in bone resorption through the pathological induction of osteoclastogenesis.