Abstract
Leishmaniasis is endemic to the tropical and subtropical regions of the world and is transmitted by the bite of an infected sand fly. The multifaceted interactions between Leishmania, the host innate immune cells, and the adaptive immunity determine the severity of pathogenesis and disease development. Leishmania parasites establish a chronic infection by subversion and attenuation of the microbicidal functions of phagocytic innate immune cells such as neutrophils, macrophages and dendritic cells (DCs). Other innate cells such as inflammatory monocytes, mast cells and NK cells, also contribute to resistance and/or susceptibility to Leishmania infection. In addition to the cytokine/chemokine signals from the innate immune cells, recent studies identified the subtle shifts in the metabolic pathways of the innate cells that activate distinct immune signal cascades. The nexus between metabolic pathways, epigenetic reprogramming and the immune signaling cascades that drive the divergent innate immune responses, remains to be fully understood in Leishmania pathogenesis. Further, development of safe and efficacious vaccines against Leishmaniasis requires a broader understanding of the early interactions between the parasites and innate immune cells. In this review we focus on the current understanding of the specific role of innate immune cells, the metabolomic and epigenetic reprogramming and immune regulation that occurs during visceral leishmaniasis, and the strategies used by the parasite to evade and modulate host immunity. We highlight how such pathways could be exploited in the development of safe and efficacious Leishmania vaccines.
Highlights
Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a spectrum of vector-borne neglected diseases affecting over 12 million people worldwide with growing geographical extension [1, 2]
The immune response to Leishmania infection is primarily initiated by innate immune cells which orchestrate the generation of protective innate and adaptive immunity against Leishmania parasites
While the role of the innate immune cells in host protection during Leishmania infection are being explored, important questions regarding their roles in shaping the protective immunity in a prophylactic vaccine setting remain to be investigated
Summary
Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a spectrum of vector-borne neglected diseases affecting over 12 million people worldwide with growing geographical extension [1, 2]. Leishmania parasites have evolved highly successful strategies to evade the microbicidal activity of neutrophils, to prime infected macrophages towards an anti-inflammatory/alternative phenotype, and to undermine the Th1 polarizing functions of DCs, thereby attenuating the host protective adaptive immune responses [9,10,11]. These altered immunological characteristics of the host cells upon infection are often induced by changes in the host metabolic pathways. This review attempts to highlight the role of the innate immune cells, the metabolomic and epigenetic reprogramming, and immune regulation during VL, and discuss their implications with respect to the development of a vaccine against VL
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