Soluble CD 163 masks fibronectin‐binding protein A ‐mediated inflammatory activation of S taphylococcus aureus infected monocytes

Summary Binding to fibronectin ( FN ) is a crucial pathogenic factor of S taphylococcus aureus mediated by fibronectin‐binding protein A ( FnBP ‐ A ) and extracellular adherence protein ( Eap ). Recently, we have shown that binding of soluble CD 163 ( sCD 163) to FN linked to these molecules exhibits anti‐microbial effects by enhancing phagocytosis and killing activity of S . aureus ‐infected monocytes. However, it remained unclear whether sCD 163 also influences the monocytic activation status. Using genetically modified staphylococcal strains we now identified FnBP ‐ A , but not Eap , as activator of the inflammatory response of monocytes to infection. FnBP ‐ A ‐mediated inflammatory activation was masked by sCD 163 binding to S . aureus promoting efficient pathogen elimination. Thus, sCD 163 protects monocytes from overwhelming activation upon staphylococcal infection by dampening the secretion of pro‐inflammatory cytokines TNF α, IL ‐1β, IL ‐6 and IL ‐8 and DAMP molecule MRP 8/14. Moreover, sCD 163 limited expression of pro‐apoptotic transcription factor NR4A1 induced during S . aureus infection and inhibited induction of chemokine CXCL 2promoting survival of staphylococci in vivo . sCD 163‐mediated effects were not due to general immunosuppression since MAP kinase activation and ROS production were unaltered during infection of monocytes with sCD 163‐bound bacteria. Thus, sCD 163 promotes a specific defence of the immune system against FnBP ‐ A ‐mediated inflammatory activation enabling successful pathogen elimination, tissue recovery and resolution of inflammation.