Innate immunity againstLeishmaniainfections

Abstract

Leishmaniasis is a major health problem that affects more than 300 million people throughout the world. The morbidity associated with the disease causes serious economic burden in Leishmania endemic regions. Despite the morbidity and economic burden associated with Leishmaniasis, this disease rarely gets noticed and is still categorized under neglected tropical diseases. The lack of research combined with the ability of Leishmania to evade immune recognition has rendered our efforts to design therapeutic treatments or vaccines challenging. Herein, we review the literature on Leishmania from innate immune perspective and discuss potential problems as well as solutions and future directions that could aid in identifying novel therapeutic targets to eliminate this parasite.

Leishmania vaccine development: exploiting the host–vector–parasite interface

“…Distinctively, salivary antigens induce a robust T cell response in mice without adjuvant (49). Specific adjuvant molecules may directly activate innate immune receptors, for example, Toll-like receptors (TLRs) (50, 51). Other formulation systems may include both delivery and immunostimulatory components.…”

AIM2 inflammasome is associated with disease severity in tegumentary leishmaniasis caused by Leishmania (V.) braziliensis

“…During initial phases of Leishmania infection, innate immune cells such as macrophages, neutrophils and dendritic cells secrete inflammatory mediators that subsequently drive adaptive immunity . Activation of innate immunity by pathogens or cellular stresses (PAMPs or DAMPs) is mediated by pattern recognition proteins such as Toll‐like receptors (TLRs) and nucleotide‐binding domain and leucine‐rich repeat‐containing (NLR) proteins . Numerous studies suggest that innate immunity is a pivotal mechanism in parasite control.…”

Immune responses against protozoan parasites: a focus on the emerging role of Nod-like receptors

“…Leishmania lipophosphoglycan (LPG), glycoproteins, and DNA activate TLR2, TLR4, and TLR9 signaling, respectively [72–76]. More importantly, activation of TLR2, TLR4, or TLR9 by their respective antigens results in significant protection from Leishmania pathogenesis and parasite burden [77]. Additionally, the results of recent studies show a surprising role for eosinophils and mast cells in inducing proper immune responses against Leishmania and in providing protection, mostly through the regulation of DCs and adaptive immunity [78,79].…”

“…Whether increased IL-4 production results in a reduction in IFN-γ or whether IL-18 directly inhibits IFN-γ production by negatively regulating T-bet needs to be further examined. As reviewed elsewhere, these discrepancies in outcomes could be directly due to the differences in Leishmania strains or mouse genotypes tested [77]. …”