Mycobacterium leprae infection disrupts the vitamin D-mediated antibacterial response (INM3P.362)

Abstract

Abstract Leprosy is a debilitating disease caused by infection with Mycobacterium leprae (mLEP). Patients diagnosed with leprosy present on a spectrum of disease characterized by disseminated lepromatous leprosy (L-lep) at one end and self-limiting tuberculoid leprosy (T-lep) at the other end. Previous studies have demonstrated the role of the vitamin D (vit D) system in mediating the antibacterial response to mycobacterial infection; however, it is not understood how dysregulation of the vit D system contributes to disease outcomes. The present study investigates the factors that regulate vit D metabolism and activation in leprosy. Monocytes were infected with mLEP and analyzed for vit D system gene expression and metabolism. In contrast to stimulation with synthetic toll-like receptor 2 (TLR2) ligand, mLEP infection did not induce production of the biologically active form of vit D. Furthermore, gene expression of activating enzyme 1α-hydroxylase (CYP27B1) and vit D receptor (VDR) were not induced by infection. Conversely, treatment with irradiated mLEP induced expression of CYP27B1 and VDR. This suggests that infection does not stimulate the vit D intracrine system in the same manner described for TLR2-sensing of mycobacterial peptides. Instead, infection triggers mechanisms that repress vit D metabolism. Moreover, mLEP-infected T-lep-associated macrophages are resistant to this repression. This study highlights the role of the vit D system in the host response to mLEP infection.