Interestingly, the first-line TB drug rifampicin activates PXR, which can impair its effectiveness in infected macrophages, underscoring the complex interactions between NRs and drug efficacy.440,441 Rifampicin, a first-line anti-tuberculosis (TB) drug, is a potent activator of PXRs, which in turn compromises the effect of rifampicin in M. tuberculosis-infected human macrophages.442. Here, NR1I2 is linked to tuberculosis.