The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the
antimicrobial peptides and
proteins present in the airway surface fluid (ASF), the
mucin-rich fluid covering the respiratory epithelium. These include larger
proteins such as
lysozyme and
lactoferrin, as well as the cationic
defensin and
cathelicidin peptides. While some of these
peptides, such as human
beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by
Toll-like receptor-mediated pathways. These
peptides can act as
microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of
antimicrobial peptide activity or gene expression can result in increased susceptibility to
infections. This has been observed with
cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of
peptides in the airway. Pathogenic
virulence factors can inhibit
defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in
infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of
peptide gene expression in animal models, as well as the optimization of
peptide-based
therapeutics shows promise for the treatment and prevention of airway
infectious diseases.