Neutrophil characterization for the development of novel combination therapy in a murine model of influenza pneumonia with secondary pneumococcal coinfection

Abstract

Pneumococcal coinfection is a critical complication of influenza pneumonia and has played a vital role in the lethal synergism seen in influenza pandemics throughout the last century. This project focuses on identifying novel combination therapy which targets the excessive innate immune response in addition to the pathogens involved to improve clinical outcome. In order to develop this therapy model, a consistent and appropriate murine model for dual infection is established and the availability of chemokine receptors as potential targets is evaluated. Finally, a CXCR2 antagonist, Sch527123, is tested in combination therapy in this model and shows promise when used in combination and when administered near the start of clinical disease. This research provides the foundation for the exciting potential of innate immune targets to treat pneumococcal coinfection in pandemics.