IgG immune complexes with Staphylococcus aureus protein A enhance osteoclast differentiation and bone resorption by stimulating Fc receptors and TLR2. (12th November 2019)

• Record Type: Journal Article
• Authors: Kamohara, Asana; Hirata, Hirohito; Xu, Xianghe; Shiraki, Makoto; Yamada, Sakuo; Zhang, Jing-Qi; Kukita, Toshio; Toyonaga, Kenji; Hara, Hiromitsu; Urano, Yasuteru; Yamashita, Yoshio; Miyamoto, Hiroshi; Kukita, Akiko
• Is Part Of: International immunology. Volume 32:Number 2(2020)
• Page Start: 89
• Page End: 104
• Publication Date: 2019-11-12
• Subjects: osteoclastogenesis -- osteomyelitis -- pro-inflamatory cytokine; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxz063
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : How S. aureus ICs promote bone resorption Abstract: Staphylococcus aureus is a main pathogen of osteomyelitis and protein A is a virulence factor with high affinity for IgG. In this study, we investigated whether S. aureus affects the differentiation and bone resorption of osteoclasts through the IgG-binding capacity of protein A. Staphylococcus aureus pre-treated with serum or IgG showed marked enhancement in osteoclastogenesis and bone resorption compared to non-treated S. aureu s or a protein A-deficient mutant. Blocking of the Fc receptor and deletion of the Fcγ receptor gene in osteoclast precursor cells showed that enhanced osteoclastogenesis stimulated by S. aureus IgG immune complexes (ICs) was mediated by the Fc receptor on osteoclast precursor cells. In addition, osteoclastogenesis stimulated by S. aureus ICs but not the protein A-deficient mutant was markedly reduced in osteoclast precursor cells of Myd8 8-knockout mice. Moreover, NFATc1, Syk and NF-κB signals were necessary for osteoclastogenesis stimulated by S. aureus ICs. The results suggest the contribution of a of Toll-like receptor 2 (TLR2)-Myd88 signal to the activity of S. aureus ICs. We further examined the expression of pro-inflammatory cytokines that is known to be enhanced by FcγR-TLR cross-talk. Osteoclasts induced by S. aureus ICs showed higher expression of TNF-α and IL-1β, and marked stimulation of proton secretion of osteoclasts activated by pro-inflammatory cytokines. Finally, injection of S. aureus, but not the protein A-deficient mutant, exacerbated bone loss in implantation and intra-peritoneal administration mouse models. Our results provide a novel mechanistic aspect of bone loss induced by S. aureus in which ICs and both Fc receptors and TLR pathways are involved.