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Updated: Apr 17, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
MyD88 in macrophages is critical for abscess resolution in staphylococcal skin infection
Reinhild Feuerstein1, Maximilian Seidl2, Marco Prinz3
1Center for Chronic Immunodeficiency, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany;
Abstract:
When Staphylococcus 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 (Mϕ) contributes to both timely escalation and termination of PML-mediated inflammation in a mouse model of staphylococcal skin infection. Mϕs were key to recruit PML within hours in response to staphylococci, irrespective of bacterial viability. In contrast with bone marrow-derived Mϕs, dermal Mϕs 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 Mϕs were missing or functionally impaired. In normal mice, clearance of the infection and contraction of the PML infiltrate were accompanied by expansion of resident Mϕs in a CCR2-dependent fashion. Thus, whereas monocytes were dispensable for the early immune response to staphylococci, they contributed to Mϕ renewal after the infection was overcome. Taken together, MyD88-dependent sensing of staphylococci by resident dermal Mϕs is key for a rapid and balanced immune response, and PMLs are dependent on intact Mϕ for full function. Renewal of resident Mϕs requires both local control of bacteria and inflammatory monocytes entering the skin.
Insights
Myeloid differentiation primary response gene 88 (MyD88)-dependent sensing by dermal macrophages is crucial for initiating and resolving inflammation during Staphylococcus aureus skin infections. Polymorphonuclear leukocytes (PMLs) require macrophages for effective bacterial clearance.
Area of Science:
- Immunology
- Dermatology
- Microbiology
Background:
- Staphylococcus aureus skin infections lead to abscess formation involving polymorphonuclear leukocytes (PMLs).
- The molecular mechanisms regulating inflammation initiation and resolution in skin infections are not fully understood.
- Myeloid differentiation primary response gene 88 (MyD88) deficiency is linked to severe staphylococcal infections.
Purpose of the Study:
- To investigate the role of MyD88-dependent sensing by dermal macrophages in orchestrating inflammation during Staphylococcus aureus skin infection.
- To elucidate the mechanisms of PML recruitment, activation, and clearance in response to S. aureus.
- To understand the contribution of monocytes and resident macrophages to the immune response and resolution.
Main Methods:
- Utilized a mouse model of staphylococcal skin infection.
- Investigated the activation of dermal macrophages and PMLs.
- Assessed the role of MyD88, UNC-93B, TLR2, and CCR2 in the immune response.
- Examined the impact of macrophage deficiency or impairment on infection clearance.
Main Results:
- MyD88-dependent sensing of S. aureus by dermal macrophages controlled both the escalation and termination of PML-mediated inflammation.
- Dermal macrophages, unlike bone marrow-derived macrophages, activated independently of UNC-93B or TLR2.
- PMLs were activated in an MyD88-independent manner but required functional macrophages for effective bacterial clearance.
- Monocytes were dispensable for the early response but contributed to macrophage renewal post-infection via CCR2.
Conclusions:
- MyD88-dependent sensing by resident dermal macrophages is essential for a balanced immune response to S. aureus skin infections.
- Polymorphonuclear leukocytes rely on intact macrophages for their full function in combating infection.
- Macrophage renewal after infection resolution depends on bacterial control and the influx of inflammatory monocytes.
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