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

DELPINO M VICTORIA; BARRIONUEVO PAULA; MACEDO COSTA GILSON; COSTA OLIVEIRA SERGIO; DI GENARO SILVIA; SCIAN ROMINA; MIRAGLIA M CRUZ; FOSSATI CARLOS A; BALDI PABLO C; GIAMBARTOLOMEI GUILLERMO H

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2012 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 TNF-a-elicited osteoclastogenesis in response to B. abortus infection. Culture supernatant (CS) from macrophages infected with B. abortus induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Although B. abortus-infected macrophages actively secreted IL-1β, IL-6 and TNF-a, osteoclastogenesis depended on TNF-a since CS from B. abortus infected macrophages failed to induce osteoclastogenesis in BMM from TNF receptor (TNFR) 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 may be involved in bone resorption through the pathological induction of osteoclastogenesis.