ESAT-6 has been shown to directly bind to the TLR2 receptor, inhibiting downstream signal transduction. It has also been studied that the inactivation of ESAT-6 leads to decreased virulence of M. tuberculosis.
ESAT-6's interaction with the TLR2 receptor impairs downstream signaling, which is also reflected in its impact on the virulence of M. tuberculosis when it is inactivated.