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Identification of chicken cathelicidin-2 core elements involved in antibacterial and immunomodulatory activities

By A. van Dijk, E.M. Molhoek, E.J.A. Veldhuizen, Hanne Tjeerdsma - van Bokhoven, E. Wagendorp, F. Bikker and H.P. Haagsman


The biological functions of avian cathelicidins are poorly defined. Inmammals,cathelicidins have shownto possess potent broad-range antimicrobial activity aswell as immunomodulatory activities. Therefore,we investigated the microbicidal activities and localization of Cathelicidin-2 in non-infected and Salmonellachallenged 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 heterophilswas observed in the jejunum of Salmonella enteritidis-challenged broilers within 8 h post-infection. Heterophilswere shownto 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 heterophilmediated release, cathelicidins may greatly contribute to avian innate immunity

Topics: Antimicrobial peptide, Cathelicidin, Chicken, Heterophils, Innate Immunity, Salmonella enteritidis
Year: 2009
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