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),...

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Bibliographic Details
Published in:Cell host & microbe 2009-09, Vol.6 (3), p.231-243
Main Authors: Yuk, Jae-Min, Shin, Dong-Min, Lee, Hye-Mi, Yang, Chul-Su, Jin, Hyo Sun, Kim, Kwang-Kyu, Lee, Zee-Won, Lee, Sang-Hee, Kim, Jin-Man, Jo, Eun-Kyeong
Format: Article
Language:English
Subjects:
Antimicrobial Cationic Peptides - genetics
Antimicrobial Cationic Peptides - immunology
Autophagy - drug effects
Cells, Cultured
Cholecalciferol - pharmacology
Host-Pathogen Interactions
Humans
Macrophages - cytology
Macrophages - drug effects
Macrophages - microbiology
Monocytes - cytology
Monocytes - drug effects
Monocytes - microbiology
Mycobacterium tuberculosis - physiology
Tuberculosis - genetics
Tuberculosis - immunology
Tuberculosis - microbiology
Tuberculosis - physiopathology
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Summary: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.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2009.08.004