Paradoxical immune response in leishmaniasis: The role of toll‐like receptors in disease progression

Toll‐like receptors (TLRs), members of pattern recognition receptors, are expressed on many cells of the innate immune system, and their engagements with antigens regulate specific immune responses. TLRs signalling influences species‐specific immune responses during Leishmania infection; thus, TLRs play a decisive role towards elimination or exacerbation of Leishmania infection. To date, there is no single therapeutic or prophylactic approach that is fully effective against leishmaniasis. An in‐depth understanding of the mechanisms by which Leishmania species evade, or exploit host immune machinery could lead to the development of novel therapeutic approaches for the prevention and management of leishmaniasis. In this review, the role of TLRs in the induction of a paradoxical immune response in leishmaniasis was discussed. This review focuses on highlighting the novel interplay of TLR2‐ /TLR9‐driven resistance or susceptibility to 5 clinically important Leishmania species in human. The activation of TLR2/TLR9 can induce diverse anti‐Leishmania activities depending on the species of infecting Leishmania parasite. Infection with L. infantum and L. mexicana initiates TLR2/9 activation leading to host protective immune response, while infection with L. major, L. donovani and L. amazonensis trigger either a TLR2‐ /9‐related protective or non‐protective immune responses. These findings suggest that TLR2 and TLR9 are targets worth pursuing either for modulation or blockage to trigger host protective immune response towards leishmaniasis.