Neutrophil bioenergetics and function in pneumonia and sepsis
Research type
Research Study
Full title
Does aerobic glycolysis exaggerate age related neutrophil dysfunction in community acquired pneumonia and sepsis: time for a new therapeutic strategy?
IRAS ID
270130
Contact name
David Thickett
Contact email
Sponsor organisation
University of Birmingham
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Research Summary
Pneumonia is a severe lung infection and a leading cause of death, especially in older people. Older people who survive pneumonia are more likely to need readmission to hospital, have a poorer quality of life and reduced independence.
We know that the immune system does not function normally in older people, and this impaired function is worse during a severe infection.
Neutrophils are the most numerous white blood cells and are key to fighting infections such as pneumonia. Neutrophils circulate in the blood stream but then move to areas of infection in the body, eating bacteria and releasing toxic products. The neutrophils ability to do this is impaired in older adults and is especially impaired when sepsis is present.
We think this poor function is due to an impairment of a fundamental process within the cell, such as metabolism. Metabolism describes the process by which a cell takes up glucose and converts this to energy. This may be the cause of the blunted responses we see in older adults with severe infections.
To investigate this, I intend to recruit older and younger adults who are admitted to hospital with pneumonia to my study. I will take blood samples from them on enrollment, 3-5 days later and then six weeks later to assess their neutrophil function at the start of pneumonia and as they recover. I will assess neutrophil metabolism and then I will then test if using new treatments which target metabolism can improve the neutrophil’s ability to migrate towards and kill bacteria in a test tube.
I will compare these results to older adults without pneumonia. This will give me evidence and data to progress to human studies with the eventual aim of developing a therapy that can improve neutrophil function in older adults, and thus improve survival.Summary of Results
Pneumonia is a common and serious illness in older adults, often leading to hospitalization and even death. This study aimed to investigate whether the immune system functions effectively in older individuals during pneumonia. Neutrophils, a type of white blood cell crucial for fighting infections, are found to be less efficient in older adults, struggling to move to the infection site.
The research discovered that in older adults with severe pneumonia, neutrophils exhibited reduced accuracy in migration compared to their healthy counterparts. Additionally, the study found that the neutrophils of individuals with pneumonia had a diminished ability to produce essential factors for killing bacteria. This indicates that in older adults with pneumonia, white blood cells face challenges reaching the infection site and are less effective in clearing bacteria.
Examining the metabolism of neutrophils, which is their ability to generate energy, the study revealed that energy generation remained consistent in pneumonia cases compared to the control group. This suggests that the issues with migration and bacterial killing are not linked to a lack of energy in the cells. Furthermore, a comparison of neutrophil metabolism in older adults with and without pneumonia showed impaired energy metabolism in older individuals, regardless of infection status. This finding is noteworthy because it suggests that the decline in neutrophil function associated with aging may be linked to a failure in energy generation.
The researchers aim to publish these findings in an accessible journal, providing valuable insights for scientists to build upon. The goal is to deepen our understanding of how the immune system changes with age and explore potential strategies for targeting the immune system to enhance outcomes in infections
REC name
Wales REC 3
REC reference
19/WA/0299
Date of REC Opinion
3 Dec 2019
REC opinion
Further Information Favourable Opinion