title: Importance of Endosomal Cathelicidin Degradation To Enhance DNA-Induced Chicken Macrophage Activation.
abstract: Cathelicidins are essential in the protection against invading pathogens through both their direct antimicrobial activity and their immunomodulatory functions. Although cathelicidins are known to modulate activation by several TLR ligands, little is known about their influence on DNA-induced macrophage activation. In this study, we explored the effects of cathelicidins on DNA-induced activation of chicken macrophages and elucidated the intracellular processes underlying these effects. Our results show that chicken cathelicidin (CATH)-2 strongly enhances DNA-induced activation of both chicken and mammalian macrophages because of enhanced endocytosis of DNA-CATH-2 complexes. After endocytosis, DNA is liberated from the complex because of proteolytic breakdown of CATH-2, after which TLR21 is activated. This leads to increased cytokine expression and NO production. Through the interaction with DNA, CATH-2 can play an important role in modulating the immune response at sites of infection. These observations underline the importance of cathelicidins in sensing bacterial products and regulating immune responses.
authors.affiliation: Division of Molecular Host Defence, Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands; and.
authors.forename: Maarten
authors.initials: M
authors.lastname: Coorens
authors.affiliation: Division of Molecular Host Defence, Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands; and.
authors.forename: Albert
authors.initials: A
authors.lastname: van Dijk
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, 1081 LA Amsterdam, the Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Bikker
authors.affiliation: Division of Molecular Host Defence, Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands; and.
authors.forename: Edwin J A
authors.initials: EJ
authors.lastname: Veldhuizen
authors.affiliation: Division of Molecular Host Defence, Faculty of Veterinary Medicine, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, the Netherlands; and H.P.Haagsman@uu.nl.
authors.forename: Henk P
authors.identifier: http://orcid.org/0000-0002-4931-5201
authors.initials: HP
authors.lastname: Haagsman
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D030161:Avian Proteins / Q000276:immunology*; D002460:Cell Line; D002645:Chickens; D004247:DNA / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D011992:Endosomes / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D059748:Proteolysis; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D030161:Avian Proteins; D004247:DNA; D054804:Cathelicidins