title: Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin.
abstract: Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Yuk
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.forename: Chul-Su
authors.initials: CS
authors.lastname: Yang
authors.forename: Hyo Sun
authors.initials: HS
authors.lastname: Jin
authors.forename: Kwang-Kyu
authors.initials: KK
authors.lastname: Kim
authors.forename: Zee-Won
authors.initials: ZW
authors.lastname: Lee
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology*; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000502:physiology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D002762:Cholecalciferol; D054804:Cathelicidins