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
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Cell Host Microbe. 2009 Sep 17;6(3):231-43. doi: 10.1016/j.chom.2009.08.004.
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.
自噬和维生素D3介导的先天免疫已被证明可提供针对细胞内结核分枝杆菌感染的保护作用。在此，我们表明这两种抗分枝杆菌防御机制通过人cathelicidin（hCAP-18/LL-37）（一种抗菌蛋白cathelicidin家族的成员）的调节功能在生理上相互关联。我们表明，维生素D的活性形式1,25-二羟基维生素D3（1,25D3）通过cathelicidin在人单核细胞中诱导自噬，cathelicidin激活了自噬相关基因Beclin-1和Atg5的转录。1,25D3还以cathelicidin依赖的方式诱导人巨噬细胞中分枝杆菌吞噬体与自噬体的共定位。此外，由生理水平的1,25D3介导的人巨噬细胞中的抗分枝杆菌活性需要自噬和cathelicidin。这些结果表明，具有直接抗菌活性的人cathelicidin也可作为维生素D3诱导自噬的介质。
