IAV/bacteria coinfection causes changes in pathology in an in vitro model of the lung epithelium

Abstract Infection by the Influenza A Virus (IAV) remains a persistent issue contributing to increased risk of morbidity and mortality, especially for susceptible individuals. IAV infection can lead to increased susceptibility to bacterial infections, which further exacerbate disease. Therapeutics targeting pathogens are often ineffective as pathogens can mutate to avoid potential vaccines and antimicrobials. Improving our understanding of IAV/bacteria-host interactions can allow us to improve host-specific approaches to tackle potential morbidity and mortality brought on by coinfections that are primarily found in epithelial cells. Lung epithelial cells not only serve as an integral part of the respiratory system, but are also crucial in host defense against respiratory infections. Therefore, we adopted an Air-Liquid Interface (ALI) strategy for the culture of human bronchial epithelial cells (HBEC) to mimic the structure and function of respiratory epithelial tissue. ALI cultures were then subjected to single and coinfections by IAV and Streptococcus pneumoniaeto assess the resulting pathology. We discovered that the specific type of infection influenced the type of programmed cell death that occurred, ranging from apoptotic to necroptotic. Additionally, coinfection with IAV and bacteria caused a unique gene expression profile. These findings demonstrate that the presence of specific pathogens causes a significant change in the cell death characteristics as well as transcriptional profile of lung epithelial cells. We hope that the progress of our investigation further elucidates consequences of host-pathogen interactions that can contribute to developing novel therapeutic strategies for complex lung infections. Supported by grants from the NIH, NHLBI R01HL126887 (A.J.), P20GM121344 Pilot Project (A.J.), and under award number RL5GM118975 (R.Z.) of NIGMS.