Chicken heterophils are recruited to the site of Salmonella infection and release antibacterial mature Cathelicidin-2 upon stimulation with LPS.

The biological functions of avian cathelicidins are poorly defined. In mammals, cathelicidins have shown to possess potent broad-range antimicrobial activity as well as immunomodulatory activities. Therefore, we investigated the microbicidal activities and localization of Cathelicidin-2 in non-infected and Salmonella-challenged broiler chickens. Using immunohistochemistry, Cathelicidin-2 was shown to be abundantly present in heterophils, localized in the large rod-shaped granules, but absent in other peripheral blood cells and intestinal epithelial cells. Cathelicidin-2 synthesis was observed to be initiated at the early promyelocyte stage. Considerable infiltration of Cathelicidin-2 containing heterophils was observed in the jejunum of Salmonella enteritidis-challenged broilers within 8 h post-infection. Heterophils were shown to release mature Cathelicidin-2 peptide upon stimulation with Salmonella-derived LPS in a time-dependent way. Processing of the Cathelicidin-2 precursor was mediated by serine proteases with a divalent cation dependency. Cathelicidin-2 peptide showed potent bactericidal and fungicidal activity against all tested microorganisms, including chicken-specific Salmonella isolates. These results underscore the importance of avian heterophils as a first line of defence against invading pathogens and implicate that via heterophil-mediated release, cathelicidins may greatly contribute to avian innate immunity.

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