Pediatric Musculoskeletal Infection: Hijacking the Acute-Phase Response

Tissue injury activates the acute-phase response mediated by the liver, which promotes coagulation, immunity, and tissue regeneration. To survive and disseminate, musculoskeletal pathogens express virulence factors that modulate and hijack this response. As the acute-phase reactants required by these pathogens are most abundant in damaged tissue, these infections are predisposed to occur in tissues following traumatic or surgical injury. Staphylococcus aureus expresses the virulence factors coagulase and von Willebrand binding protein to stimulate coagulation and to form a fibrin abscess that protects it from host immune-cell phagocytosis. After the staphylococcal abscess community reaches quorum, which is the colony density that enables cell-to-cell communication and coordinated gene expression, subsequent expression of staphylokinase stimulates activation of fibrinolysis, which ruptures the abscess wall and results in bacterial dissemination. Unlike Staphylococcus aureus, Streptococcus pyogenes expresses streptokinase and other virulence factors to activate fibrinolysis and to rapidly disseminate throughout the body, causing diseases such as necrotizing fasciitis. Understanding the virulence strategies of musculoskeletal pathogens will help to guide clinical diagnosis and decision-making through monitoring of acute-phase markers such as C-reactive protein, erythrocyte sedimentation rate, and fibrinogen.