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.
JournalJournal of leukocyte biology
J Leukoc Biol (1938-3673)
Instituto de Estudios de la Inmunidad Humoral (CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
J Leukoc Biol. 2012 Feb;91(2):285-98
Español | English
© Galenicom 1999-2013