engleski

The long pentraxin PTX3 at the host‐pathogen interface in Staphylococcus aureus‐dependent osteomyelitis

Osteomyelitis (OM) is a debilitating infection of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). SA exploits several strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms are largely unclear. Here we studied the SA/bone interface with a focus on the soluble pattern recognition molecule long pentraxin 3 (PTX3), which is emerging as a new player in bone physiology and pathology. A murine model of SA intrabone infection was developed that recapitulates surgery/trauma‐OM in humans. Local and systemic infection and inflammation were assessed by means of flow cytometry, RT‐PCR, ELISA, histochemistry, and microCT. At 14 days from SA challenge, >95% of mice developed infection in the injected limb only, which underwent extensive remodeling with loss of trabecular and apposition of periosteal bone. Larger bacterial burdens were found in the bone of WT than in that of PTX3 KO mice at 6 and 14 days from infection. Accordingly, WT animals had more severe inflammation, in terms of expansion of innate immune cells in the spleen, and increase of inflammatory cytokines in the serum. Also, PTX3 levels were augmented in SA‐ infected mice in the serum and bone. Genetic deficiency of PTX3 protects from infection in a murine model of locally‐induced SA‐ OM. Our findings point to an involvement of this long pentraxin in the pathogenesis of OM, and open unforeseen windows on the molecular mechanisms of this disease, with therapeutic and diagnostic potentials

animal models ; infectious disease ; innate host defence ; innate immunity ; tissue damage and repair

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