Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 10, Pages 7115-7120Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.10.7115
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Funding
- NIAID NIH HHS [K22 AI085025] Funding Source: Medline
- NIAMS NIH HHS [R01 AR050626-05, R01 AR050626] Funding Source: Medline
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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/IL 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. The Journal of Imunology, 2008, 181: 7115-7120.
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