Defensins and the peptide LL‑37 are natural proteins made by immune cells and airway lining cells that kill germs and help control inflammation in the lungs. This review explains the different types of defensins, their broad antimicrobial actions, and how they also recruit immune cells and can calm inflammation. It notes that LL‑37 works similarly, but we still need to figure out exactly how much each contributes to lung health.

Defensins were first identified in 1985 and are now recognized as part of a large family of antimicrobial peptides, divided into three categories: alpha-, beta-, and -defensins. These defensin classes differ in structure, sites of expression and biological activities. Human alpha-defensins include peptides that are expressed primarily in neutrophils, whereas human beta-defensins are widely expressed in epithelial cells, including those lining the respiratory tract. Defensins were first studied for their broad spectrum activity against bacteria, fungi and viruses; however, it is now clear that they also recruit inflammatory cells and promote innate and adaptive immune responses. Recent evidence shows that defensins have anti-inflammatory effects as well. Hence, defensins can participate in all phases of an immune response in the lung, including initial killing of pathogens and mounting - and resolution -- of an immune or inflammatory response. The cathelicidin, LL-37, is an antimicrobial peptide produced by neutrophils and respiratory epithelial cells that has similar roles in lung immunity as the defensins. A major challenge for the coming years will be to sort out the relative contributions of defensins and LL-37 to overall immune responses in the lung and to determine which of their many in vitro activities are most important for lung immunity.