New insights into the life cycle, host cell tropism, and infection amplification of Leishmania spp.

The genus Leishmania comprises several species of digenetic protozoan parasites that cause a spectrum of diseases known as leishmaniases, which are transmitted to humans and other mammals through the bite of hematophagous female sand flies. Leishmania spp. and their invertebrate vectors are widely distributed across the globe, putting more than a billion people at risk. Once inside mammalian hosts, these intracellular parasites reside within parasitophorous vacuoles of host cells. Although macrophages are the primary infected cells in lesions, Leishmania can also infect other cell types, whose roles in maintaining the parasite's life cycle and contributing to pathogenesis remain unclear. Similarly, the processes governing parasite dissemination from the initial infection site in the skin to internal organs, as well as the mechanisms driving the infection of new cells, are still under investigation. In this review, we underscore some existing gaps in Leishmania's life cycle, discussing i) the various cell types that serve as host cells for the parasite and their potential roles in the disease, ii) the mechanisms that might contribute to infection amplification, iii) the strategies possibly involved in dissemination and visceralization, iv) the mechanisms driving the generation of super-infective vectors, and v) the occurrence of a mating stage in the cycle. Altogether, these aspects may reshape our perspective on the basic biology of Leishmania, deepening our understanding of the host-parasite relationship and hopefully opening avenues toward a better understanding of the disease.