Defining the mechanisms underlying reduced immunity to Streptococcus pneumoniae with age

Abstract

The increase in the elderly population is impacting the social and economic aspects of the modern world as increasing longevity is not matched by an increasing healthy lifespan. Increased infections are a major component of ill health in old age. The aged immune system fails to respond properly to many infections such as pneumonia, caused mainly by the bacterium Streptococcus pneumoniae, which is responsible for high rates of death among the elderly. Here we studied the impact of age on the function of neutrophils, immune cells crucial for immunity to S. pneumoniae. Blood from healthy young (n=3, <30 years) and elderly (n=3, >65 years) volunteers was stimulated by antibody or complement-bound live or dead S. pneumoniae serotype 4 (TIGR4 strain). The amount of bacteria taken up by neutrophils and their production of reactive oxygen species (ROS), used to kill bacteria, was measured by flow-cytometry. The ability of neutrophils to trap S. pneumoniae extracellularly using a web made of extruded DNA (neutrophil extracellular traps, NETs) was also analysed by counting the remaining viable bacteria after incubation with neutrophils. We found that elderly neutrophils phagocytosed and produced ROS less well in response to S. pneumoniae, but this could be overcome if complement was bound to the bacteria. Although only n=1, preliminary data showed that NETs trapping of S. pneumoniae was lower (40%) in the elderly compared to young neutrophils (57%). Our data indicate that neutrophils from the elderly can produce ROS and phagocytose S. pneumoniae but may have impaired NET trapping ability.