期刊
PLOS PATHOGENS
卷 8, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1003017
关键词
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资金
- NIAID, NIH [AI084573]
- International Maternal Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network
- National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- National Institute of Mental Health (NIMH) [AI068632]
- Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]
- Pediatric AIDS Clinical Trials Group (PACTG)
- IMPAACT Group [U01 AI068616]
- National Institute of Allergy and Infectious Diseases (NIAID)
- NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network
- NICHD [N01-DK-9-001/HHSN267200800001C]
Toll-like receptors (TLR) are important in recognizing microbial pathogens and triggering host innate immune responses, including autophagy, and in the mediation of immune activation during human immunodeficiency virus type-1 (HIV) infection. We report here that TLR8 activation in human macrophages induces the expression of the human cathelicidin microbial peptide (CAMP), the vitamin D receptor (VDR) and cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1), which 1 alpha-hydroxylates the inactive form of vitamin D, 25-hydroxycholecalciferol, into its biologically active metabolite. Moreover, we demonstrate using RNA interference, chemical inhibitors and vitamin D deficient media that TLR8 agonists inhibit HIV through a vitamin D and CAMP dependent autophagic mechanism. These data support an important role for vitamin D in the control of HIV infection, and provide a biological explanation for the benefits of vitamin D. These findings also provide new insights into potential novel targets to prevent and treat HIV infection.
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