Pneumonia caused by the bacterium Streptococcus pneumoniae (pneumococcus) kills more than half a million children worldwide annually. Little is known about heritable host immune determinants that predispose some children to severe pneumococcal disease. In mice, Dr. Morley found that loss of L-plastin—a protein that controls cell motility and regulates immune responses—results in rapid death from respiratory pneumococcal infection. This led to the hypothesis that defects in proteins functioning in the same molecular pathway will increase pneumococcal susceptibility. To test this hypothesis, DNA samples from patients with pneumococcal disease will be compared to those from healthy family members to define mutations that predispose individuals to severe pneumococcal disease.
• Establish a database of patient samples from an unvaccinated country (Papua New Guinea) and from a vaccinated region (St. Louis) to define the kind of pneumococcus that causes infection
• Use DNA samples from patients in the database to identify genetic differences that impair the immune response and predispose individuals to pneumococcal infection
Potential impact: Defining the genetic determinants that regulate the host immune response is essential for the development of new therapies to prevent or treat severe pneumococcal disease and possibly other pediatric lung diseases.