title: Interspecies cathelicidin comparison reveals divergence in antimicrobial activity, TLR modulation, chemokine induction and regulation of phagocytosis.
abstract: Cathelicidins are short cationic peptides initially described as antimicrobial peptides, which can also modulate the immune system. Because most findings have been described in the context of human LL-37 or murine CRAMP, or have been investigated under varying conditions, it is unclear which functions are cathelicidin specific and which functions are general cathelicidin properties. This study compares 12 cathelicidins from 6 species under standardized conditions to better understand the conservation of cathelicidin functions. Most tested cathelicidins had strong antimicrobial activity against E. coli and/or MRSA. Interestingly, while more physiological culture conditions limit the antimicrobial activity of almost all cathelicidins against E. coli, activity against MRSA is enhanced. Seven out of 12 cathelicidins were able to neutralize LPS and another 7 cathelicidins were able to neutralize LTA; however, there was no correlation found with LPS neutralization. In contrast, only 4 cathelicidins enhanced DNA-induced TLR9 activation. In conclusion, these results provide new insight in the functional differences of cathelicidins both within and between species. In addition, these results underline the importance not to generalize cathelicidin functions and indicates that caution should be taken in extrapolating results from LL-37- or CRAMP-related studies to other animal settings.
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Coorens
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Maaike R
authors.initials: MR
authors.lastname: Scheenstra
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Edwin J A
authors.initials: EJ
authors.lastname: Veldhuizen
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D054804:Cathelicidins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010587:Phagocytosis / Q000187:drug effects*; D000067996:RAW 264.7 Cells; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D054804:Cathelicidins; D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors