Tuberculosis (TB) is a devastating illness. In the search for novel anti-TB therapies, there is growing interest in host-directed therapy (HDT), which seeks to synergize with frontline antibiotics by altering the host conditions – making us a less hospitable host – and re-sensitizing the bacteria to antibiotic therapy. This dissertation project lies at the intersection between two understudied fields: host-pathogen interactions and sphingolipids during Mycobacterium tuberculosis infection.