Understanding the innate immune response to the Mycobacterium tuberculosis, is a key step to development of effective immunotherapies for tuberculosis (TB). Epidemiological evidence correlates low serum vitamin A (retinol) levels to active TB; however, retinol is biologically inactive. Previously, we demonstrated that stimulation of M. b-infected macrophages with the active vitamin A hormone, all-trans retinoic acid (ATRA), triggers a NPC2-dependent antimicrobial activity. Therefore, understanding the mechanism by which the immune system metabolizes and activates retinol at the site of infection will solve the mystery of how retinol, despite being biologically inactive, can influence the immune response to infection. Through gene expression and functional analysis of human macrophage subsets and dendritic cells (DCs) we identified that GM-CSF-derived DCs express enzymes capable of the two step conversion of retinol into ATRA including, ALDH1A2 and DHRS9, which is subsequently released from the cell. Conditioned medium, from DCs cultured with retinol, stimulated expression of NPC2 from monocytes which was inhibited by a retinoic acid receptor inhibitor (RARi). Inclusion of DEAB, an ALDH1A2 inhibitor, during DCs and retinol incubation also abrogated this response. Expression levels of vitamin A metabolic enzymes are lower in TB lung tissues compared with normal lung. These results help us incorporate vitamin A into clinical care and therapeutic modalities for TB.