Building the Lung's Defenses Against Infection
Faculty Profile: Henry Akinbi, Pulmonary Biology
Can an antimicrobial protein first identified more than 80 years ago hold the key to protecting newborns -- and children with cystic fibrosis -- from dangerous infections?
NIH-funded research led by Henry Akinbi, MD, in the Division of Pulmonary Biology at Cincinnati Children's, seeks to identify the role of lysozyme in pulmonary host defense. Discovered by Sir Alexander Fleming, lysozyme is an enzyme that degrades components of the cell wall in bacteria. It is abundant in body secretions.
With pathogens showing increased resistance to antibodies, Dr. Akinbi and his colleagues believe that boosting lysozyme levels may be one way to augment the body's natural defenses, because the body is unlikely to develop resistance to natural proteins. Children who are susceptible to lung infections -- particularly premature infants and children with cystic fibrosis -- would benefit.
When Dr. Akinbi and his colleagues expressed a high level of lysozyme in the lungs of transgenic mice, they discovered the mice were highly resistant to acute lung infection. They were protected from contracting group B Streptococcus, the most important pathogen in newborns, as well as Pseudomonas aeruginosa, a common and sometimes deadly pathogen in children with cystic fibrosis.
Conversely, the researchers recently discovered that mice deficient in the major isoform of lysozyme were more susceptible to lung infection by Klebsiella pneumoniae, a common cause of pneumonia in both newborns and older children. This was surprising, because these mice were replete with the other major host defense proteins in the lungs, surfactant proteins A and D.
These findings are helping scientists understand how the normal host defense mechanism can be subverted by a pathogen and provide insight into the workings of the body's innate immune system in vivo. The ultimate goal is to identify potential therapeutic manipulations to use as adjuncts to current antimicrobial strategies.
Currently, Dr. Akinbi is collaborating with Timothy Weaver, PhD, a colleague at Cincinnati Children's, and a German pulmonologist, to test ways to deliver lysozyme effectively and non-invasively to the lungs of mice. Using nebulizers, the researchers have increased lysozyme activity in the airways 2½-fold for up to eight hours in mice with no adverse side effects. They are testing whether this increase is adequate to protect against common causes of pneumonia by enhancing bacterial clearance, decreasing bacterial colonization in the airways -- or both.
