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

Journal of Leukocyte Biology

Romina Scian³  Sergio Costa Oliveira¹  Guillermo H. Giambartolomei, ³  Gilson Costa Macedo¹  Pablo C. Baldi and³  Paula Barrionuevo³  Silvia Di Genaro⁴  M. Cruz Miraglia²  Carlos A. Fossati³  M. Victoria Delpino³ 

[1] Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil; Laboratorio de Inmunogenética, Hospital de Clínicas œJosé de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;Instituto de Estudios de la Inmunidad Humoral (CONICET), Facultad de Farmacia y Bioquímica, and  Laboratorio de Inmunogenética, Hospital de Clínicas œJosé de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;Instituto de Investigaciones Biológicas-San Luis (CONICET), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina  Laboratorio de Inmunogenética, Hospital de Clínicas œJosé de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;

关键词: osteoclast;    bone;    inflammation;    bacteria;    lipoprotein;    innate immunity;   

DOI  :  10.1189/jlb.04111185

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-α-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-1β, IL-6, and TNF-α, osteoclastogenesis depended on TNF-α, 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-α, 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.

【 授权许可】

Unknown