Calvin Phan

Introduction. The influenza virus causes contagious respiratory illness that infect the nose, throat and lungs. IAV affects millions of people every year and can lead to severe illnesses and lead to death in those that are immunocompromised. Following infection from influenza, surface glycoproteins (GP96) and signaling pathways are modified leading to increased susceptibility to deadly secondary infection specifically from bacterial pneumonia^1,3,4. Exploration into various changes in lung pathology can be a useful target for development of therapeutic techniques to prevent superinfection^5-7. Methods. Eight to ten-week-old mice were intranasally inoculated with 250 plaque forming units (PFU) of PR8 in 50 μL PBS, under light isoflurane anesthesia. The mice were then inoculated with S. pneumoniae four days post IAV infection⁸. Results. Upon inspection of lung tissue, IAV co-infection significantly increased the total bacterial burden of the mice, when compared to just pneumoniae infection alone⁸. A majority of secondary infections are chronic in nature, therefore early detection is very important to prevent large scale damage of lung tissue through disease progression^5-6. Conclusion. GP96, a surface glycoprotein functions as an exacerbation factor to promote colonization from secondary infection, leading to dysfunction of lung and barrier responses. GP96 has also been shown to interact with TLRs, critical for bacterial entry into cells¹. Plasma GP96 levels that were positively correlated with interleukin-6 levels were significantly elevated in COVID-19 patients admitted to the hospital¹. Using this data, it is possible to detect rising levels of interleukin-6 in hospitalized patients. This is important for early detection of secondary infection of respiratory diseases. Once early detection has been made, immunotherapy with Interleukin-22 has been shown to have anti-inflammatory and anti-infection benefits^2,9. In the current study, exogenous treatment of IAV infected mice with IL-22 reduces bacterial dissemination. This is because IL-22 has been demonstrated to modulate the gene expression profile that reinforces tissue integrity of the lungs. This clinical study can highlight treatments to improve patient outcomes and recovery following post-influenza bacterial superinfection to prevent fatal systemic bacterial invasion and excessive lung tissue damage.

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8. Chen, Y.-Y., Huang, C.-T., Li, S.-W., Pan, Y.-J., Lin, T.-L., Huang, Y.-Y., Li, T.-H., Yang, Y.-C., Gong, Y.-N., & Hsieh, Y.-C. (2021). Bacterial factors required for streptococcus pneumoniae coinfection with influenza A virus. Journal of Biomedical Science, 28(1). https://doi.org/10.1186/s12929-021-00756-0
9. Barthelemy, A., Sencio, V., Soulard, D., Deruyter, L., Faveeuw, C., Le Goffic, R., & Trottein, F. (2018). Interleukin-22 immunotherapy during severe influenza enhances lung tissue integrity and reduces secondary bacterial systemic invasion. Infection and Immunity, 86(7). https://doi.org/10.1128/iai.00706-17