Considering the central role of macrophages in both pathogenesis and clearance of infection and the potential of synthetic TLR7/8 agonists as both antiparasitic and immunomodulatory agents, the present study builds on previous work in CL to provide the first systematic evaluation of a panel of 11 well-characterized imidazoquinoline-based TLR7/8 agonists against VL caused by L. donovani. Here, TLR7 is linked to infection.