Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis

Abstract

The intracellular protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a vector-borne disease of major public health concern, estimated to affect 12 million people worldwide. The clinical manifestations of leishmaniasis are highly variable and can range from self-healing localized cutaneous lesions to life-threatening disseminated visceral disease. Once introduced into the skin by infected sandflies, Leishmania parasites interact with a variety of immune cells, such as neutrophils, monocytes, dendritic cells (DCs), and macrophages. The resolution of infection requires a finely tuned interplay between innate and adaptive immune cells, culminating with the activation of microbicidal functions and parasite clearance within host cells. However, several factors derived from the host, insect vector, and Leishmania spp., including the presence of a double-stranded RNA virus (LRV), can modulate the host immunity and influence the disease outcome. In this review, we discuss the immune mechanisms underlying the main forms of leishmaniasis, some of the factors involved with the establishment of infection and disease severity, and potential approaches for vaccine and drug development focused on host immunity.

Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility to Leishmania infection

“…Notably, parasite and host genetics regulating visceralization and virulence of VL-causing species are clearly distinct from those regulating these mechanisms in CL-causing species [104] . For instance, the A2 gene locus has been demonstrated to be important for visceralization of VL caused by L. donovani and L. infantum , but in L. major and L. tropica causing CL, A2 is a pseudogene [105] , [106] . Similarly, natural resistance-associated macrophage protein 1/Lsh (NRAMP/Lsh) gene located in chromosome 1, a cation transporter, controls susceptibility to L. donovani but not to L. major [107] .…”

Development and Characterization of PLGA Nanoparticles Containing 17-DMAG, an Hsp90 Inhibitor

“…Among the cutaneous presentations, mucocutaneous leishmaniasis (MCL), caused mainly by L. aethiopica in the Old World and L. braziliensis in the New World, is the most debilitating form, with destructive lesions occurring on the palate, lips and nasal septum (Akhoundi et al, 2016;Burza et al, 2018;WHO, 2020a). The most common form, localized cutaneous leishmaniasis (LCL), is caused by a variety of parasite species, including L. major, L. tropica, and L. aethiopica in the Old World, in addition to L. braziliensis, L. guyanensis, L. amazonensis, and L. mexicana in the New World (Kaye and Scott, 2011;Masmoudi et al, 2013;Burza et al, 2018;Meira and Gedamu, 2019). Despite not being fatal, LCL can affect patients' quality of life according to the evolution and spread of skin lesions, social stigmatization, psychological effects, and absenteeism (Carvalho et al, 1994;Scorza et al, 2017;Burza et al, 2018).…”

Antileishmanial Activity and Influence on Mitochondria of the Essential Oil from Tagetes lucida Cav. and Its Main Component

“…Approximately, 0.7-1 million new cases of leishmaniasis occur per year and 12 million infected people worldwide are reported from nearly 100 endemic countries. The clinical manifestations of leishmaniasis are highly variable with two main clinical forms-cutaneous leishmaniasis and visceral leishmaniasis, which range from self-healing localized cutaneous lesions to life-threatening disseminated visceral disease [1,2]. So far, the development of an effective Leishmania vaccine for humans with effective immune protection has not yet been achieved [3].…”