TLRs in Mycobacterial Pathogenesis: Black and White or Shades of Gray

Toll-like receptors (TLRs) play critical role in the innate recognition of pathogens besides orchestrating innate and adaptive immune responses. These receptors exhibit exquisite specificity for different pathogens or their products and, through a complex network of signalling, generate appropriate immune responses. TLRs induce both pro- and anti-inflammatory signals depending on interactions with the adapter molecules thereby impacting the outcome of infection. Hence, TLR signalling ought to be stringently regulated to avoid harmful effects on the host. Mycobacteria express antigens which are sensed by TLRs leading to activation of various signalling molecules important for initiating the death of infected cells and containment of pathogens. Conversely, it also utilizes TLRs for immune evasion and persistence. Due to the enormous diversity in the repertoire of virulence traits expressed by mycobacteria, genetic variations in TLRs often impair the host's ability to respond to mycobacterial-stress, affecting health and disease manifestations. Thus, understanding TLR signalling is of great importance for insights into host-mycobacterial interactions and designing effective measures for controlling the spread and persistence of the bacterium.