Innate immune defense mechanisms in the lung upon bacterial infection: Submucosal glands, antimicrobial peptides and Toll-like receptors

Cystic fibrosis (CF) is one of the most common fatal genetic diseases in Caucasians affecting approximately 30,000 children and adults in the United States. It is caused by a mutation in cystic fibrosis transmembrane conductance regulator (CFTR). 85 percent of patients died of Lung disease. The lungs are histologically normal at birth; patients soon acquire bacterial infection that is difficult to clear due to breach in the innate immune defense. Chronic infection and inflammation lead to lung destruction and respiratory failure. The goal of my research is to investigate the innate immune defense mechanism in the lung specifically Submucosal glands, antimicrobial peptides and Toll like receptors. It is found that submucosal glands contribute to innate immunity in the lung by affecting the affect both the ionic composition and bioelectric properties of the airway. It also secretes antimicrobial peptide. Antimicrobial peptides (hBD2, mBD3 and LL-37/hCAP18) are found to express in the airway. hBD2 and synthetic LL-37/hCAP18 have antimicrobial activity toward several bacterial and synergic with other peptides. HBD2 and mBD3 are upregulated upon challenging with bacterial products. These suggested these antimicrobial peptides might play role in the innate immune defense in the lung upon bacterial infection. Human TLR2 was shown to mediate up-regulation of hBD2 through NF-κB signal transduction pathway. Mouse TLR4 was shown to play a critical role of TLR4 in mediating an effective innate immune response to H. influenzae in the lung. In summary, it is shown that submucosal glands, antimicrobial; peptides and Toll like receptors may play role in the innate immunity in the lung.