Vitamin D-dependent cathelicidin inhibits Mycobacterium marinum infection in human monocytic cells.
Sato. Emi E; Imafuku. Shinichi S; Ishii. Kazunari K; Itoh. Ryota R; Chou. Bin B; Soejima. Toshinori T; Nakayama. Juichiro J; Hiromatsu. Kenji K
Key Findings
- Active vitamin D strongly raises LL‑37 levels in human monocyte cells
- Both vitamin D and added LL‑37 peptide markedly reduce Mycobacterium marinum replication in these cells
- The antimicrobial effect requires functional autophagolysosomes; inhibitors erase the benefit
Practical Outcomes
- Keeping vitamin D levels sufficient may enhance your body’s innate defenses via LL‑37, and experimental use of LL‑37 peptide could be considered for antimicrobial support, though current data are limited to cell‑culture studies. No specific dosing or safety data are provided, so further research is needed before applying this in real‑world protocols.
Summary
Vitamin D (the active form 1,25‑OH2D3) triggers immune cells to make more of the natural antibiotic peptide LL‑37, which then helps the cells kill a TB‑like bacteria by boosting their internal recycling system (autophagy). Adding either vitamin D or synthetic LL‑37 cuts bacterial growth in lab‑grown monocytes, and blocking autophagy stops this benefit.
Abstract
1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates the production of human cathelicidin antimicrobial peptide (CAMP) from monocytes/macrophages infected with Mycobacterium tuberculosis (M. tbc). CAMP facilitates the co-localization of autophagolysosomes with M. tbc, promoting the antimicrobial activity of monocytes. Mycobacterium marinum (M. marinum) is an acid-fast bacillus that causes less severe granulomatous skin lesions compared with M. tbc. We investigated whether autophagic antimicrobial activity is promoted by 1,25(OH)2D3 or C-terminal of cathelicidin LL-37 in human monocytes upon infection with M. marinum. Human monocytes (THP-1) were infected with M. marinum. Effects of simultaneous treatments of 1,25(OH)2D3, exogenous LL-37 peptide, autophagolysosome inhibitors, 3-methyladenine or chloroquine, were examined. CAMP was strongly induced by adding 1,25(OH)2D3 to the culture of THP-1 cells. In the absence of 1,25(OH)2D3 M. marinum infection alone did not induce CAMP, however, simultaneous addition of 1,25(OH)2D3 to M. marinum infection accelerated CAMP production more than 1,25(OH)2D3 alone. Proliferation of M. marinum was markedly decreased in the presence of 1,25(OH)2D3 or exogenous LL-37 in THP-1 cells. Co-localization of CAMP with autophagolysosome was evident in 1,25(OH)2D3 and LL-37 treated THP-1 cells after M. marinum infection. Autophagolysosome inhibitors abrogated the antimicrobial effects of 1,25(OH)2D3 and exogenous LL-37 against M. marinum infection in THP-1 cells. Human monocytic cells, whose CAMP production is up-regulated by 1,25(OH)2D3-vitamin D receptor pathway, accelerate antimicrobial function of autophagolysosome in M. marinum infection.
Study Information
pubmed
2013
2013-02-09T00:00:00.000Z
10.1016/j.jdermsci.2013.01.011
42
30