In evolutionary well-established host–parasite systems, such as visceral leishmaniasis (VL) caused by Leishmania spp., TLR4 detects glycosphingophospholipid derived from L. donovani and the proteoglycolipid complex (P8GLC) from L. pifanoi, enhancing the production of proinflammatory cytokines. This evidence concerns the gene TLR4 and visceral leishmaniasis.