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Port d'Entrée for Respiratory Infections - Does the Influenza A Virus Pave the Way for Bacteria?
Nikolai Siemens1,2, Sonja Oehmcke-Hecht3, Thomas C Mettenleiter4
1Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
Abstract:
Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health.
Insights
Respiratory co-infections pose a global health threat. This review explores current experimental models for studying bacterial and viral respiratory infections, proposing improved human-relevant models for better translation of findings.
Area of Science:
- Infectious Diseases
- Microbiology
- Respiratory Medicine
Background:
- Bacterial and viral co-infections of the respiratory tract are a significant global health concern.
- Common upper respiratory tract bacteria like *Staphylococcus aureus*, *Streptococcus pneumoniae*, and *Streptococcus pyogenes* can disseminate to the lower respiratory tract, causing severe pneumonia, often following viral infections such as Influenza A virus (IAV).
Purpose of the Study:
- To review current knowledge on respiratory bacterial and viral co-infections.
- To evaluate existing experimental models used for studying these co-infections.
- To propose novel, human-relevant models for improved research translation.
Main Methods:
- Review of existing literature on respiratory co-infection models.
- Analysis of common animal models, including mice, ferrets, rats, guinea pigs, rabbits, and non-human primates.
- Discussion of limitations in current animal models for human disease translation.
Main Results:
- Traditional animal models, particularly mice, are widely used but have limitations in accurately reflecting human disease.
- Existing models have contributed to understanding infectious disease mechanisms.
- Significant gaps remain in translating findings from animal models to human clinical outcomes.
Conclusions:
- Human engineered lung tissue, human *ex vivo* lung tissue, and porcine models are proposed as superior alternatives for studying respiratory co-infections.
- These novel models offer greater potential for translating research findings to human health.
- Adoption of these models could improve understanding and treatment of respiratory co-infections, benefiting both animal and human health.