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

Hidenori Matsui, Yuriko Nakatani, Haruno Yoshida, Asako Takizawa, Osamu Takeuchi, Anders Øverby, Takashi Takahashi, Somay Y. Murayama, Koichi Matsuo

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 × 105 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 significantly inhibited osteoclast formation and bone resorption. These data suggest that increased expression of RANKL in heterogeneous bone marrow cells provoked bone destruction during GAS infection.

Original languageEnglish
Pages (from-to)1390-1404
Number of pages15
JournalCellular Microbiology
Volume18
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

Fingerprint

Streptococcus pyogenes
Cytoplasmic and Nuclear Receptors
Eating
Ligands
Bone and Bones
Infection
Streptococcus
Transgenic Mice
Osteoclasts
Bone Marrow Cells
Extremities
T-Lymphocytes
Necrotizing Fasciitis
Osteoprotegerin
Bone Resorption
Septic Shock
Osteogenesis
Stem Cells
Fibroblasts
Monoclonal Antibodies

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Flesh-eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor-κB ligand. / Matsui, Hidenori; Nakatani, Yuriko; Yoshida, Haruno; Takizawa, Asako; Takeuchi, Osamu; Øverby, Anders; Takahashi, Takashi; Murayama, Somay Y.; Matsuo, Koichi.

In: Cellular Microbiology, Vol. 18, No. 10, 01.10.2016, p. 1390-1404.

Research output: Contribution to journalArticle

Matsui, H, Nakatani, Y, Yoshida, H, Takizawa, A, Takeuchi, O, Øverby, A, Takahashi, T, Murayama, SY & Matsuo, K 2016, 'Flesh-eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor-κB ligand', Cellular Microbiology, vol. 18, no. 10, pp. 1390-1404. https://doi.org/10.1111/cmi.12581
Matsui, Hidenori ; Nakatani, Yuriko ; Yoshida, Haruno ; Takizawa, Asako ; Takeuchi, Osamu ; Øverby, Anders ; Takahashi, Takashi ; Murayama, Somay Y. ; Matsuo, Koichi. / Flesh-eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor-κB ligand. In: Cellular Microbiology. 2016 ; Vol. 18, No. 10. pp. 1390-1404.
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