Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin.
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.
Yuk
Jae-Min
JM
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Shin
Dong-Min
DM
Lee
Hye-Mi
HM
Yang
Chul-Su
CS
Jin
Hyo Sun
HS
Kim
Kwang-Kyu
KK
Lee
Zee-Won
ZW
Lee
Sang-Hee
SH
Kim
Jin-Man
JM
Jo
Eun-Kyeong
EK
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
D023181:Antimicrobial Cationic Peptides; D002762:Cholecalciferol; D054804:Cathelicidins