Regulatory T cell-neutrophil interaction in the development and maintenance of secondary pneumonia

Secondary bacterial pneumonia after influenza is a significant, worldwide health problem. Secondary infections were responsible for many deaths in the pandemics of 1918 and 2009. These infections also occur with seasonal influenza and with other respiratory viruses. It is striking that the bacteria that cause these infections commonly live harmlessly in patients’ throats beforehand, and it is unclear how this changes to cause disease.

In previous work I have identified several ways by which systemic inflammation can impair white blood cell function. The aim of this project is to evaluate whether these also facilitate secondary pneumonia and allow colonising bacteria to  cause disease. The goals are to determine whether blocking a key signalling molecule (PI3K delta) can prevent development of secondary pneumonia, and to explore the mechanisms by which influenza can impair white blood cells, looking at numbers and function of specific cell types. I will also set up a more life-like model of secondary infection arising from colonising bacteria and explore the changes in the microbes found in the lung (‘lung microbiome’) during infection, and how these may relate to secondary pneumonia.

The ultimate aim is to develop novel, non-antibiotic strategies for preventing and treating secondary pneumonia.