MyD88 in Macrophages Is Critical for Abscess Resolution in Staphylococcal Skin Infection

摘要

When S taphylococcus aureus penetrates the epidermis and reaches the dermis, polymorphonuclear leukocytes (PMLs) accumulate and an abscess is formed. However, the molecular mechanisms that orchestrate initiation and termination of inflammation in skin infection are incompletely understood. In human myeloid differentiation primary response gene 88 (MyD88) deficiency, staphylococcal skin and soft tissue infections are a leading and potentially life-threatening problem. In this study, we found that MyD88-dependent sensing of S. aureus by dermal macrophages (M?) contributes to both timely escalation and termination of PML-mediated inflammation in a mouse model of staphylococcal skin infection. M?s were key to recruit PML within hours in response to staphylococci, irrespective of bacterial viability. In contrast with bone marrow–derived M?s, dermal M?s did not require UNC-93B or TLR2 for activation. Moreover, PMLs, once recruited, were highly activated in an MyD88-independent fashion, yet failed to clear the infection if M?s were missing or functionally impaired. In normal mice, clearance of the infection and contraction of the PML infiltrate were accompanied by expansion of resident M?s in a CCR2-dependent fashion. Thus, whereas monocytes were dispensable for the early immune response to staphylococci, they contributed to M? renewal after the infection was overcome. Taken together, MyD88-dependent sensing of staphylococci by resident dermal M?s is key for a rapid and balanced immune response, and PMLs are dependent on intact M? for full function. Renewal of resident M?s requires both local control of bacteria and inflammatory monocytes entering the skin.