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.
van Dijk
Albert
A
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Tersteeg-Zijderveld
Monique H G
MH
Tjeerdsma-van Bokhoven
Johanna L M
JL
Jansman
Alfons J M
AJ
Veldhuizen
Edwin J A
EJ
Haagsman
Henk P
HP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002645:Chickens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011201:Poultry Diseases / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012477:Salmonella enteritidis / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C504855:CMAP27 protein, chicken; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054804:Cathelicidins