Abstract
An essential function of the innate immune system is to directly trigger antimicrobial mechanisms to defend against invading pathogens. In humans, one such pathway involves activation by TLR2/1L leading to the vitamin D-dependent induction of antimicrobial peptides. In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin. Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin. Finally, IL-15-differentiated macrophages could be triggered by 25D3 to induce an antimicrobial activity against intracellular Mycobacterium tuberculosis. Therefore, IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway.
| Original language | English |
|---|---|
| Pages (from-to) | 7115-20 |
| Number of pages | 6 |
| Journal | Journal of Immunology |
| Volume | 181 |
| Issue number | 10 |
| Publication status | Published - 15 Nov 2008 |
Keywords
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
- Antimicrobial Cationic Peptides
- Cell Differentiation
- Gene Expression
- Humans
- Interleukin-15
- Macrophages
- Receptors, Calcitriol
- Reverse Transcriptase Polymerase Chain Reaction
- Toll-Like Receptor 1
- Toll-Like Receptor 2
- Vitamin D
