Toll-Like Receptor 8 Ligands Activate a Vitamin D Mediated Autophagic Response that Inhibits Human Immunodeficiency Virus Type 1

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. © 2012 campbell,spector.