Combination drug treatment for tuberculosis (TB) can extend over 6 months which provides the perfect setupfor the development of drug resistant strains of M. tuberculosis (M.tb). With approximately 2 million new casesof TB each year, short course drug therapy would rapidly reduce the burden of M.tb infection and havesignificant impact on global public health. Targeting host responses during TB drug treatment is a novelapproach to provide quicker and more effective drug treatment for TB. We hypothesize that IL-10 is the driverof the reported immune dampening properties of PZA, and that modification of IL-10 can be exploited toshorten the drug treatment time for M.tb infection. Our hypothesis is built upon preliminary data showing thatPZA can clear M.tb infection to sterilization in IL-10 deficient mice within 45 days, a significant shortening oftreatment time. We propose experiments to establish the causal relationship between PZA and IL-10 thataccelerates the clearance of M.tb infection. These include blocking the action of IL-10 in vivo and investigatingimmune function during infection with a PZA resistant strain of M.tb. At the completion of these studies we willhave determined the specific mechanism for how the anti-mycobacterial action of PZA is accelerated on an IL-10 deficient background.
With approximately 2 million new cases of TB each year; short course drug therapy would rapidly reduce theburden of M.tb infection and have significant impact on global public health. Targeting host responses duringTB drug treatment is a novel approach to provide quicker and more effective drug treatment for TB.
