Cathelicidins are
peptide components of the innate immune system of mammals. Apart from exerting a direct
antibiotic activity, they can also trigger specific defense responses in the host. Their roles in various pathophysiological conditions have been studied, but there is a lack of published information on their expression and activities in the context of
mastitis. The aims of this study were to investigate the expression of the bovine
cathelicidins BMAP-27,
BMAP-28, Bac5, and
indolicidin in healthy and infected mammary tissue and in
lipopolysaccharide (LPS)-treated cells, to determine their activities against bacteria isolated from
bovine mastitis, and to examine their potentials to trigger defense responses in bovine mammary cells. The genes were found to be upregulated in LPS-stimulated neutrophils, but not in infected quarters or epithelial cells. All
peptides showed a variably broad spectrum of activity against 28 bacterial isolates from
bovine mastitis (MIC values, 0.5 to 32 microM), some of which were
antibiotic resistant. The activity of each
peptide was significantly enhanced when it was pairwise tested with the other
peptides, reaching the synergy threshold when
indolicidin was present. The bactericidal activity was sensitive to milk components;
BMAP-27 and -28 were highly effective in mastitic bovine milk and inhibited in milk from healthy cows. Both
peptides were also active in whey and in blood serum and triggered the expression of
tumor necrosis factor alpha (
TNF-alpha) in bovine mammary epithelial cells. Our results indicate multiple roles for the bovine
cathelicidins in
mastitis, with complementary and mutually enhanced antimicrobial activities against causative pathogens and the capacity to activate host cells.