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Updated: Feb 4, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and
Liana C Chan1,2, Maura Rossetti3,4, Lloyd S Miller5
1Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90502.
Abstract:
Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Our prior studies discovered a role for protective innate memory against recurrent methicillin-resistant S. aureus (MRSA) SSSI. In the present study, the dynamics and mechanisms of this response were explored in recurrent SSSI in WT mice. Priming by prior infection reduced skin lesion severity and MRSA burden, and protected against dissemination at day 7 but not day 2. Cytokine and cellular signatures in SSSI differed at day 2 versus 7, and were distinct in skin versus blood or spleen. Cytokines associated with protection in skin included increased IL-17, IL-6, monokine inducible by IFN-γ (MIG), and RANTES, while increased IP-10 correlated with protection from dissemination. Cellular signatures of protection included increased Th17, M1 macrophage, and dendritic cell populations in abscesses, and total macrophages in lymph nodes. Priming potentiated S. aureus-specific phagocytic killing by bone marrow-derived macrophages in vitro, and their adoptive transfer into naïve skin afforded protective efficacy in vivo. Present findings indicate that protective immunity in recurrent S. aureus infection is locally targeted, and involves specific memory conferred by macrophages. These insights provide targets for vaccine and immunotherapeutic development against MRSA.
Insights
Prior infection primes the immune system, reducing severity and spread of Staphylococcus aureus skin infections. Macrophages play a key role in this protective memory, offering targets for new MRSA therapies.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Staphylococcus aureus is a leading cause of skin and skin structure infections (SSSI).
- Prior studies identified innate memory conferring protection against recurrent methicillin-resistant S. aureus (MRSA) SSSI.
- The dynamics and mechanisms of this protective response require further elucidation.
Purpose of the Study:
- To explore the dynamics and mechanisms of protective innate memory in recurrent SSSI caused by S. aureus in wild-type (WT) mice.
- To characterize the cytokine and cellular signatures associated with protection at different time points and anatomical sites.
- To investigate the role of macrophages in mediating protective immunity against S. aureus.
Main Methods:
- Induction of recurrent SSSI in WT mice.
- Analysis of cytokine profiles and cellular populations in skin, blood, and spleen at days 2 and 7 post-infection.
- In vitro assessment of S. aureus-specific phagocytic killing by bone marrow-derived macrophages.
- In vivo adoptive transfer of macrophages into naïve skin.
Main Results:
- Prior infection reduced SSSI severity and bacterial burden, protecting against dissemination at day 7 but not day 2.
- Distinct cytokine and cellular signatures were observed at day 2 versus day 7, and varied between skin, blood, and spleen.
- Key protective cytokines included IL-17, IL-6, MIG, RANTES, and IP-10.
- Cellular signatures of protection involved increased Th17 cells, M1 macrophages, dendritic cells in abscesses, and macrophages in lymph nodes.
- Primed macrophages demonstrated enhanced S. aureus-specific phagocytic killing in vitro and conferred protection in vivo.
Conclusions:
- Protective immunity against recurrent S. aureus infection is locally targeted.
- Macrophages confer specific memory crucial for protection.
- These findings identify potential targets for vaccine and immunotherapeutic development against MRSA.
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