Our study identified unique gene signatures (IL-27, STAT1, IRF1, TLR4, IL-15, IL-2RA, IL-24, TGFβ, CD28, CD80, NFATC1, and PTGDR2) that discriminate active pulmonary TB from uninfected controls using unstimulated PBMCs. Here, TLR4 is linked to pulmonary tuberculosis.