Flesh-eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor-κB ligand

Cellular Microbiology
Hidenori MatsuiKoichi Matsuo

Abstract

Human CD46 is a receptor for the M protein of group A streptococcus (GAS). The emm1 GAS strain GAS472 was isolated from a patient suffering from streptococcal toxic shock-like syndrome. Human CD46-expressing transgenic (Tg) mice developed necrotizing fasciitis associated with osteoclast-mediated progressive and severe bone destruction in the hind paws 3 days after subcutaneous infection with 5 × 10(5) colony-forming units of GAS472. GAS472 infection induced expression of the receptor activator of nuclear factor-κB ligand (RANKL) while concomitantly reducing osteoprotegerin expression in the hind limb bones of CD46 Tg mice. Micro-computed tomography analysis of the bones suggested that GAS472 infection induced local bone erosion and systemic bone loss in CD46 Tg mice. Because treatment with monoclonal antibodies (mAbs) against mouse CD4(+) and CD8(+) T lymphocytes did not inhibit osteoclastogenesis, T lymphocyte-derived RANKL was not considered a major contributor to massive bone loss during GAS472 infection. However, immunohistochemical analysis of the hind limb bones showed that GAS472 infection stimulated RANKL production in various bone marrow cells, including fibroblast-like cells. Treatment with a mAb against mouse RANKL s...Continue Reading

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Citations

Aug 24, 2017·Helicobacter·Hidenori MatsuiMasahiko Nakamura
Oct 30, 2020·Frontiers in Immunology·Johann VolzkeUNKNOWN KoInfekt Study Group
Dec 15, 2020·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Haruno YoshidaHidenori Matsui

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