title: Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response that inhibits human immunodeficiency virus type 1.
abstract: 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 1α-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.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Campbell
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000276:immunology / Q000494:pharmacology*; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000276:immunology; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D018167:Receptors, Calcitriol / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000819:agonists*; D014815:Vitamins / Q000276:immunology / Q000494:pharmacology*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D008024:Ligands; D018167:Receptors, Calcitriol; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D014815:Vitamins; D015652:25-Hydroxyvitamin D 2; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D054804:Cathelicidins