Macrophage-Elicited Osteoclastogenesis in Response to Brucella abortus Infection Requires TLR2/MyD88-Dependent TNF-α Production

DELPINO, MV; BARRIONUEVO, P; COSTA-MACEDO, G; COSTA-OLIVEIRA, S; DI GENARO, S; SCIAN, R; FOSSATI, CARLOS; BALDI, PC; GIAMBARTOLOMEI, G

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; 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 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-1beta, 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 KO mice. CS from B. abortus-stimulated MyD88 KO and TLR2 KO macrophages failed to express TNF-alpha, and these CS induced no osteoclast formation compared with that of the WT or TLR4 KO 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.