Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease

Gabriel, Áurea Martins; Valério-Bolas, Ana; Palma-Marques, Joana; Mourata-Gonçalves, Patrícia; Ruas, Pedro; Dias-Guerreiro, Tatiana; Santos‐Gomes, Gabriela

doi:10.1155/2019/2603730

Cited by 58 publications

(64 citation statements)

References 114 publications

(206 reference statements)

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“…Immunity against Leishmania is complex and depends on many factors, such as genetic diversity, parasite species and isolates (27)(28)(29). Leishmania spp.…”

Section: An Overview On Anti-leishmania Immunitymentioning

confidence: 99%

Unraveling the Role of Immune Checkpoints in Leishmaniasis

Silva

Stebut

2021

Front. Immunol.

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Leishmaniasis are Neglected Tropical Diseases affecting millions of people every year in at least 98 countries and is one of the major unsolved world health issues. Leishmania is a parasitic protozoa which are transmitted by infected sandflies and in the host they mainly infect macrophages. Immunity elicited against those parasites is complex and immune checkpoints play a key role regulating its function. T cell receptors and their respective ligands, such as PD-1, CTLA-4, CD200, CD40, OX40, HVEM, LIGHT, 2B4 and TIM-3 have been characterized for their role in regulating adaptive immunity against different pathogens. However, the exact role those receptors perform during Leishmania infections remains to be better determined. This article addresses the key role immune checkpoints play during Leishmania infections, the limiting factors and translational implications.

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“…Immunity against Leishmania is complex and depends on many factors, such as genetic diversity, parasite species and isolates (27)(28)(29). Leishmania spp.…”

Section: An Overview On Anti-leishmania Immunitymentioning

confidence: 99%

Unraveling the Role of Immune Checkpoints in Leishmaniasis

Silva

Stebut

2021

Front. Immunol.

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“…There are still many gaps in the knowledge of how a protective CD4 + T cell response against Leishmania is activated, maintained, and controlled (26). In the last years it has been demonstrated that the expression of co-inhibitory receptors on activated T cells during the course of an immune response plays a pivotal role in dampening T cell activity (27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis

et al. 2020

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Cutaneous Leishmaniasis (CL) affects up to one million people every year and treatments are costly and toxic. The regulation of the host immune response is complex and the knowledge of how CD4 + T cells are activated and maintained during Leishmania infection is still limited. Current therapies aim to target programmed cell death (PD)-1 and programmed cell death ligand (PD-L)-1 in order to boost T cell activity. However, the role of the PD-1/PD-L1 axis during Leishmania infection is still unclear. In this study, we found that patients with active and post-treatment CL displayed different subsets of CD4 + PD-1 + T cells. Accordingly, L. major-infected mice upregulated PD-1 on activated CD4 + T effector cells and PD-L1 on resident macrophages and infiltrating monocytes at the site of infection. L. major-infected Pdl1 −/− mice expressed lower levels of MHCII and higher levels of CD206 on macrophages and monocytes and, more importantly, the lack of PD-L1 contributed to a reduced frequency of CD4 + Ly6C hi T effector cells and an increase of CD4 + Foxp3 + regulatory T cells at the site of infection and in draining lymph nodes. Additionally, the lack of PD-L1 was associated with lower production of IL-27 by infiltrating monocytes and lower levels of the Th1 cytokines IFN-γ and TNF-α produced by CD4 + T effector cells. Pdl1 −/− mice initially exhibited larger lesions despite having a similar parasite load. Our results describe for the first time how the interruption of the PD-1/PD-L1 axis influences the immune response against CL and suggests that this axis regulates the balance between CD4 + Ly6C hi T effector cells and CD4 + Foxp3 + regulatory T cells.

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“…The presence of multiple Leishmania species with overlapping clinical features that sometimes leads to misdiagnosis in endemic areas [ 7 ], as well as the genetic heterogeneity of the parasite [ 8 , 9 ], accentuate requirement for development of laboratory tests with high accuracy to be used for species identification of Leishmania spp. [ 10 ]. However, conventional parasitology methods have an intermediate diagnostic sensitivity on dermal aspirate samples of CL, as they are influenced by the sampling procedure, type of skin lesion, parasite load and technical personnel expertise [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Performance of a universal PCR assay to identify different Leishmania species causative of Old World cutaneous leishmaniasis

et al. 2020

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Background: The characterization of Leishmania species is important for clinical management of the diseases and the epidemiological control of the parasite distribution. Most of the published polymerase chain reaction (PCR) amplification methods lack the ability to identify all species complexes, have low performance and usually need post-PCR procedures. There is a need for improving the diagnosis of CL by development of an accurate affordable PCR method to identify all Leishmania species in clinical specimens. Methods: We designed an optimized a PCR amplifying the internal transcribed spacer 2 sequence of the ribosomal RNA gene (ITS2) aligned from different strains of CL-causing Leishmania species in the Old World. The performance of the method was evaluated on lesion samples from several CL suspected patients and the limit of detection (LOD) was determined on DNA of promastigotes from reference strains. Results: The universal PCR enabled simultaneous discrimination of L. major, L. tropica and L. infantum using one primer pair in one reaction. Stained smear microscopy and Novy-MacNeal-Nicolle (NNN) medium culture alone detected 77.27% (17/22) and 72.73% (16/22) of the positive CL samples, respectively. The PCR assay showed 100% sensitivity (22/22) (95% CI: 84.56-100%) and 100% specificity (3/3) (95% CI: 29.24-100%) for species identification on isolates from lesion scraping/exudate and 100% sensitivity (13/13) (95% CI: 75.29-100%) and 100% specificity (11/11) (95% CI: 71.51-100%) for species identification on biopsy samples of CL patients, while being capable to successfully amplify as little as 0.01-0.1 pg of Leishmania DNA from cultured promastigotes. Conclusions: We present a validated easy-to-use affordable universal PCR assay to identify the most common Old World Leishmania species causing CL. This PCR assay could be used as a sensitive/specific technique to diagnose CLcausing Leishmania species in clinical samples with high accuracy.

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Cutaneous Leishmaniasis: The Complexity of Host’s Effective Immune Response against a Polymorphic Parasitic Disease

Cited by 58 publications

References 114 publications

Unraveling the Role of Immune Checkpoints in Leishmaniasis

Unraveling the Role of Immune Checkpoints in Leishmaniasis

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis

Performance of a universal PCR assay to identify different Leishmania species causative of Old World cutaneous leishmaniasis

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