Abstract Cellular immunity to Mycobacterium tuberculosis (Mtb) requires coordinated cell migration and localization to form granulomas. In addition to chemokines and adhesion proteins, we found that Mtb infection of mouse bone marrow-derived DC or MØ upregulated expression of members of a family of neuronal guidance molecules: netrins, semaphorins, slits, and ephrins, which have been implicated in inflammation and immunity. Since netrin-1 and its receptor Unc5b cause immobilization of MØ in atherosclerotic lesions, we hypothesized that up-regulation of these molecules during Mtb infection contributes to MΦ and DC sequestration in granulomas. Using RT-qPCR, we found that netrin-1 and its receptors: Unc5b, Adora 2a, and Adora2b are up-regulated in Mtb-infected cells. Immunoblotting revealed that netrin-1 is secreted by Mtb-infected MΦ, and immunofluorescence showed netrin-1 is expressed in the lungs of Mtb infected mice. Since netrin-1 is secreted, we studied the migration of peritoneal macrophages in response to CCL19 in the presence of supernatants from Mtb-infected or uninfected MΦ and DCs. Supernatants from Mtb-infected cells inhibited MΦ migration in a netrin-1-dependent fashion. Based on these results, we hypothesize that neuronal guidance molecules contribute to granuloma formation and/or maintenance in tuberculosis.