Expression and Regulation of Antimicrobial Peptides in Mucosal Immunity

Antimicrobial polypeptides (AMPs) are effector molecules of the innate immune defense. AMPs are mainly expressed in epithelial cells and immune cells, providing the first line of defense to infection as direct antimicrobials. In addition, many AMPs display immunomodulatory functions in both the adaptive and innate immune system. Thus, a tight control of AMP-expression is necessary for a functional immune response. In this thesis the antimicrobial polypeptide armament of neutrophils (PMNs) was evaluated for its activity against four human pathogens S. aureus, H. influenzae, M. catarrhalis and C. albicans. We observed a high degree of redundancy in antimicrobial activity for a majority of the AMPs. Still, some polypeptides exhibited a more specific activity against individual pathogens. This suggests that PMNs are equipped with a repertoire of antimicrobial peptides and proteins with broad activities, underscoring the importance of PMNs in the host response. In a clinical study the expressions of cathelicidin LL-37 and α-defensins HNP1-3 were quantified in nasal fluids of patients with primary immunodeficiencies (PIDs). Healthy controls and most PID patients responded to pathogens with increased levels of AMPs in their nasal fluid. Interestingly, in patients with common variable immune deficiency (CVID) and Hyper IgE syndrome (HIES), the levels of AMPs did not increase in response to pathogens. Thus, there is a dysregulation in AMP-release in CVID and HIES patients, which may explain why these patients suffer from frequent respiratory