Figure 2.

Host metabolic networks modulate tolerance to Mtb infections. Distinct metabolic networks control the inflammatory response during Mtb infection. Small molecule activation of Sirt1 with SRT1720 inhibits NF-κβ signaling and activates AMPK and promote tolerance to Mtb. This is similar to treatment with the diabetes drug Metformin that activates AMPK to inhibit inflammation and allow the host to better tolerate persistent Mtb infections. An alternative metabolic network activated by Irg1, produces the metabolite Itaconate. Itaconate can directly restrict Mtb replication, but in vivo robustly controls tolerance by modulating the inflammatory response to persistent infection. Together these metabolic networks directly and indirectly control tolerance to Mtb infection.