A new study by the University of Liverpool reveals how resistance to bacteraemic pneumonia is provided by a unique subset of lung T regulatory cells.
Streptococcus pneumoniae (the pneumococcus) is the leading cause of community-acquired pneumonia, with a large proportion of cases developing bloodstream infections. These bacteraemic pneumonia cases are associated with a high fatality rate ranging from 20% in young adults to around 60% in the elderly, despite the wide range of antibiotics and effective vaccines.
The reasons behind why certain individuals are more susceptible to bacteraemic pneumonia have been relatively unknown for many years.
What is bacteraemic pneumonia?
Pneumonia is inflammation of the lungs caused by an infection. Many people recover in two to four weeks, but some people are at a higher risk of getting seriously ill and may require hospital treatment. It can be caused by a bacterial or viral infection and can be easily contracted following another infection such as flu or COVID-19.
Symptoms include a cough, chest pain, loss of appetite, shortness of breath and an aching body. Antibiotics are commonly prescribed for this infection.
The role of T-cells in infections
The Bacterial Pathogenesis and Immunity Group, led by Professor Aras Kadioglu at the University of Liverpool, has now discovered a subset of white blood cells in mice that confer resistance to bacteraemic pneumonia. These cells have been identified as TNFR2-expressing Tregs and are critical in the maintenance and control of frontline host immune responses when pneumococci infect the lungs.
When these special Tregs are functionally impaired or absent, the immune response to infection becomes dysregulated with excessive and uncontrolled inflammation, which then leads to tissue damage. As a result, the bacteria can spread through disrupted lung tissue barriers into the bloodstream, causing the deadly condition called sepsis.
The first author of the study published in Cell Reports, Dr Rong Xu, said: “Pneumococcal infection remains a major killer globally, despite the successful introduction of pneumococcal vaccine immunisation programmes. Elucidating the mechanisms of how resistance to infection may develop in high-risk groups offers a great opportunity for us to develop targeted novel therapies.”
The study lead, Professor Aras Kadioglu, added: “Our findings show that TNFR2 expressing Treg cells are absolutely essential in controlling inflammation in the lungs and preventing the translocation of pneumococci from lung to blood, thereby providing resistance to invasive disease. In susceptible hosts, however, these cells are either functionally impaired or absent, which predisposes them to the development of sepsis. This is a significant finding, which opens the door to potential new therapies which may target and modulate this subset of Tregs to prevent and treat severe invasive pneumococcal diseases.”
