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Updated: May 16, 2026

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Intravital two-photon microscopy of host-pathogen interactions in a mouse model of Staphylococcus aureus skin abscess
Jan Liese1, Suzan H M Rooijakkers, Jos A G van Strijp
1Program of Molecular Pathogenesis, Helen L and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York City, NY 10016, USA. jan.liese@med.uni-tuebingen.de
Abstract:
Staphylococcus (S.) aureus is a frequent cause of severe skin infections. The ability to control the infection is largely dependent on the rapid recruitment of neutrophils (PMN). To gain more insight into the dynamics of PMN migration and host-pathogen interactions in vivo, we used intravital two-photon (2-P) microscopy to visualize S. aureus skin infections in the mouse. Reporter S. aureus strains expressing fluorescent proteins were developed, which allowed for detection of the bacteria in vivo. By employing LysM-EGFP mice to visualize PMN, we observed the rapid appearance of PMN in the extravascular space of the dermis and their directed movement towards the focus of infection, which led to the delineation of an abscess within 1 day. Moreover, tracking of transferred labelled bone-marrow neutrophils showed that PMN localization to the site of infection is dependent on the presence of G-protein-coupled receptors on the PMN, whereas Interleukin-1 receptor was required on host cells other than PMN. Furthermore, the S. aureus complement inhibitor Ecb could block PMN accumulation at thesite of infection. Our results establish that 2-P microscopy is a powerful tool to investigate the orchestration of the immune cells, S. aureus location and gene expression in vivo on a single cell level.
Insights
Staphylococcus aureus skin infections trigger rapid neutrophil (PMN) recruitment. Two-photon microscopy revealed PMN migration dynamics and identified host and bacterial factors influencing this crucial immune response.
Area of Science:
- Immunology
- Microbiology
- Microscopy
Background:
- Staphylococcus aureus is a common cause of severe skin infections.
- Effective control of S. aureus infections relies on rapid neutrophil recruitment.
- Understanding neutrophil migration and host-pathogen interactions in vivo is critical.
Purpose of the Study:
- To visualize and analyze neutrophil migration dynamics during S. aureus skin infections in live mice.
- To investigate host-pathogen interactions at the single-cell level in vivo.
- To identify factors influencing neutrophil recruitment to the infection site.
Main Methods:
- Development of reporter S. aureus strains for in vivo bacterial detection.
- Intravital two-photon microscopy for real-time visualization of immune cells and bacteria.
- Use of LysM-EGFP mice to track neutrophils (PMN).
- Tracking of transferred, labeled bone-marrow neutrophils.
Main Results:
- Observed rapid extravascular migration of PMN to the S. aureus infection focus, forming an abscess within 1 day.
- Demonstrated that PMN localization depends on G-protein-coupled receptors on PMN and Interleukin-1 receptor on non-PMN host cells.
- Showed that the S. aureus complement inhibitor Ecb blocks PMN accumulation.
Conclusions:
- Intravital two-photon microscopy is a powerful tool for studying immune cell orchestration, bacterial location, and gene expression in vivo.
- Identified key host and bacterial factors regulating neutrophil recruitment during S. aureus skin infections.
- Provided new insights into the dynamics of host-pathogen interactions in real-time.

