Murine Model of Sinusitis Infection for Screening Antimicrobial and Immunomodulatory Therapies
Morgan A Alford1, Ka-Yee G Choi1, Michael J Trimble1,2
1Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Abstract:
The very common condition of sinusitis is characterized by persistent inflammation of the nasal cavity, which contributes to chronic rhinosinusitis and morbidity of cystic fibrosis patients. Colonization by opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa triggers inflammation that is exacerbated by defects in the innate immune response. Pathophysiological mechanisms underlying initial colonization of the sinuses are not well established. Despite their extensive use, current murine models of acute bacterial rhinosinusitis have not improved the understanding of early disease stages due to analytical limitations. In this study, a model is described that is technically simple, allows non-invasive tracking of bacterial infection, and screening of host-responses to infection and therapies. The model was modified to investigate longer-term infection and disease progression by using a less virulent, epidemic P. aeruginosa cystic fibrosis clinical isolate LESB65. Tracking of luminescent bacteria was possible after intranasal infections, which were sustained for up to 120 h post-infection, without compromising the overall welfare of the host. Production of reactive oxidative species was associated with neutrophil localization to the site of infection in this model. Further, host-defense peptides administered by Respimat® inhaler or intranasal instillation reduced bacterial burden and impacted disease progression as well as cytokine responses associated with rhinosinusitis. Thus, future studies using this model will improve our understanding of rhinosinusitis etiology and early stage pathogenesis, and can be used to screen for the efficacy of emerging therapies pre-clinically.
Insights
A new mouse model allows non-invasive tracking of bacterial sinusitis infections, aiding the study of early disease stages. This model helps evaluate host responses and therapies for chronic rhinosinusitis, improving understanding and treatment development.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Sinusitis involves nasal cavity inflammation, often linked to chronic rhinosinusitis and cystic fibrosis morbidity.
- Opportunistic pathogens like *Staphylococcus aureus* and *Pseudomonas aeruginosa* exacerbate inflammation, particularly with innate immune defects.
- Early pathophysiological mechanisms of sinus colonization remain unclear, and current murine models have limitations in studying early disease stages.
Purpose of the Study:
- To develop a technically simple, non-invasive murine model for tracking bacterial sinusitis infections.
- To enable screening of host responses and therapeutic interventions in early rhinosinusitis.
- To investigate longer-term infection dynamics and disease progression using a specific *P. aeruginosa* isolate.
Main Methods:
- Development of a simple intranasal infection model in mice.
- Utilized luminescent *P. aeruginosa* (LESB65) for non-invasive, sustained bacterial tracking (up to 120 h).
- Monitored host responses including neutrophil localization and reactive oxidative species production; assessed therapeutic effects of host-defense peptides.
Main Results:
- The model allowed non-invasive tracking of bacterial infections for up to 120 hours without compromising host welfare.
- Neutrophil recruitment and reactive oxidative species production were observed at the infection site.
- Host-defense peptides reduced bacterial burden, impacted disease progression, and modulated sinusitis-associated cytokine responses.
Conclusions:
- This novel murine model offers a valuable tool for studying the etiology and early pathogenesis of rhinosinusitis.
- The model facilitates pre-clinical screening of emerging therapies for bacterial sinusitis.
- Findings contribute to a better understanding of host-pathogen interactions in sinusitis and potential therapeutic strategies.
