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Updated: Apr 14, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
RNA-Seq Analysis of the Host Response to Staphylococcus aureus Skin and Soft Tissue Infection in a Mouse Model
Rebecca A Brady1, Vincent M Bruno2, Drusilla L Burns1
1Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, United States of America.
Abstract:
Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of protection for staphylococcal SSTI.
Insights
This study reveals how the host
Area of Science:
- Immunology
- Microbiology
- Genomics
Background:
- Staphylococcus aureus is a common cause of skin and soft tissue infections (SSTI).
- These infections are typically self-limiting, but the host's protective mechanisms are not fully understood.
Purpose of the Study:
- To comprehensively analyze the host transcriptome during Staphylococcus aureus SSTI.
- To gain insights into the protective immune responses that resolve these infections.
Main Methods:
- A murine model of Staphylococcus aureus SSTI was established.
- RNA sequencing (RNA-seq) was performed on infected, uninfected (challenged), and naive mouse ears at multiple time points.
- Ingenuity Pathway Analysis (IPA) was used to analyze gene expression and regulatory pathways.
Main Results:
- A robust local transcriptional response was observed at the infection site, involving over 1000 upregulated genes.
- A less pronounced systemic response was detected in non-infected ears, indicating host-wide changes.
- Regulatory pathway activation, including pro-inflammatory mediators and TH1/TH17 cytokines, occurred locally before systemically, while metabolic and anti-inflammatory pathways were repressed.
Conclusions:
- The host mounts a stable, time-invariant global response to Staphylococcus aureus SSTI.
- Understanding these transcriptional changes and pathway activations provides insight into the resolution of self-limited S. aureus infections.
- These findings may help identify immune correlates of protection against staphylococcal SSTI.
