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Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response that inhibits human immunodeficiency virus type 1.

PLoS pathogens (2012-11-21)
Grant R Campbell, Stephen A Spector
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
25-Hydroxyvitamin D2, ≥98.0% (HPLC)
Supelco
25-Hydroxyvitamin D2 solution, 50 μg/mL in ethanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
25-Hydroxyvitamin D2 solution, 5 μg/mL in ethanol, ampule of 1 mL, certified reference material, Cerilliant®

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