Description of a Murine Model of Pneumocystis Pneumonia
Adélaïde Chesnay1,2,3, Loïc Gonzalez4,5, Christelle Parent4,5
1Service de Parasitologie-Mycologie-Médecine Tropicale, Pôle Biologie Médicale, Hôpital Bretonneau, CHRU de Tours, Tours, France. adelaide.chesnay@univ-tours.fr.
Abstract:
Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P. jirovecii is the second most common fungal agent among invasive fungal infections after Candida spp. Unfortunately, there is still an inability to culture P. jirovecii in vitro, and so a great impairment to improve knowledge on the pathogenesis of Pneumocystis pneumonia. In this context, animal models have a high value to address complex interplay between Pneumocystis and the components of the host immune system. Here, we propose a protocol for a murine model of Pneumocystis pneumonia. Animals become susceptible to Pneumocystis by acquiring an immunocompromised status induced by iterative administration of steroids within drinking water. Thereafter, the experimental infection is completed by an intranasal challenge with homogenates of mouse lungs containing Pneumocystis murina. The onset of clinical signs occurs within 5 weeks following the infectious challenge and immunosuppression can then be withdrawn. At termination, lungs and bronchoalveolar lavage (BAL) fluids from infected mice are analyzed for fungal load (qPCR) and immune response (flow cytometry and biochemical assays). The model is a useful tool in studies focusing on immune responses initiated after the establishment of Pneumocystis pneumonia.
Insights
A new murine model allows researchers to study Pneumocystis pneumonia by inducing immunosuppression with steroids and intranasal fungal challenge. This model aids in understanding the immune response to this serious opportunistic fungal infection.
Area of Science:
- Medical Mycology
- Immunology
- Infectious Diseases
Background:
- Pneumocystis pneumonia (PCP) is a severe opportunistic infection caused by Pneumocystis jirovecii.
- P. jirovecii is a leading cause of invasive fungal infections, second only to Candida species.
- The inability to culture P. jirovecii in vitro hinders research into its pathogenesis.
Purpose of the Study:
- To establish and validate a reproducible murine model for studying Pneumocystis pneumonia.
- To investigate the host-pathogen interactions and immune responses during PCP development.
- To provide a valuable tool for research into novel therapeutic strategies against PCP.
Main Methods:
- Induction of immunosuppression in mice through sustained administration of steroids in drinking water.
- Experimental infection via intranasal challenge with Pneumocystis murina lung homogenates.
- Analysis of fungal load using qPCR and immune responses via flow cytometry and biochemical assays in lungs and bronchoalveolar lavage (BAL) fluid.
Main Results:
- The murine model successfully replicates key aspects of Pneumocystis pneumonia, with clinical signs appearing within 5 weeks.
- The model allows for the assessment of fungal burden and detailed characterization of the host immune response.
- Immunosuppression can be withdrawn after the establishment of infection, facilitating studies on immune reconstitution.
Conclusions:
- The developed murine model provides a robust platform for studying the pathogenesis and immune response to Pneumocystis pneumonia.
- This model is crucial for advancing our understanding of PCP and for the development of effective treatments.
- It facilitates research into the complex interplay between Pneumocystis and the host immune system in established infections.
