Search results for "Leishmania major"
showing 10 items of 46 documents
IL-17A/F in Leishmania major-resistant C57BL/6 mice.
2019
Proinflammatory IL-17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL-17A in Leishmania-susceptible BALB/c and artificial overexpression of IL-17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL-17A exhibited no phenotype, and IL-17A and IL-17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL-17A and IL-17F (IL-17A/F-/- ) in infections with Leishmania major. Interestingly, lesion volumes an…
In silico prediction of Leishmania major -specific CD8+ epitopes
2017
Infections with Leishmania (L.) major induce protective IFN-γ-dependent Th1/Tc1 immunity in C57BL/6 mice as well as in immunocompetent humans. Even though antigen-specific immunity provides lifelong immunity against reinfection, a vaccine against this pathogen does not yet exist. Here, we compared the results obtained from in silico predictions of murine CD8-specific L. major peptides using the algorithm SYFPEITHI with the number and predicted affinity of known proteins/peptides. Our results indicate that the majority of "immunodominant" epitopes of L. major have not been identified so far; thus, computer-based prediction algorithms may aid the development of an effective vaccine.
Parasite Clearance in Leishmaniasis in Resistant Animals Is Independent of the IL-23/IL-17A Axis
2015
Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases
2015
ABSTRACT Leishmaniasis is one of the major neglected tropical diseases of the world. Druggable targets are the parasite cysteine proteases (CPs) of clan CA, family C1 (CAC1). In previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin L (CL) subfamily of the papain clan CAC1. Both displayed antileishmanial activity in vitro while not showing cytotoxicity against host cells. In further investigations, the mode of action was characterized in Leishmania major . It was demonstrated that aziridines 13b and 13e mainly inhibited the parasitic cathepsin B (CB)-like CPC enzyme and, additionally, ma…
Parasites Dampen Dendritic Cell Activation to Ensure Their Survival
2017
Dendritic cells (DCs) are critical for induction of protective immunity against Leishmania major. However, DC activation occurs only several weeks after parasite transmission. Parasites synthesize a macrophage-inducible C-type lectin (Mincle) ligand. Engagement of Mincle by the parasite ligand dampens DC activation, thus delaying induction of interferon-γ-producing T cells responsible for parasite eradication.
In cutaneous leishmaniasis, induction of retinoic acid in skin-derived Langerhans cells is not sufficient for induction of parasite persistence-media…
2017
Insufficient generation of Th17 cells in IL-23p19-deficient BALB/c mice protects against progressive cutaneous leishmaniasis
2017
Healing of leishmaniasis-a parasitic skin disease-is associated with high levels of secreted interferon (IFN)γ and IL-12 in resistant C57BL/6 mice and humans. Susceptible BALB/c mice predominantly react with a Th17/Th2/Treg-related immune response and finally succumb to infection. Previously, we showed that BALB/c IL-17A-/- mice are protected against Leishmania (L.) major infections, indicating that IL-17A-predominantly produced by Th17 cells-plays an important role for disease outcome. We now investigated DC-derived cytokines and finally identified IL-23p19 as key cytokine responsible for induction of Leishmania-specific Th17 cells that play an important role for progressive disease in sus…
Impaired T-cell-dependent protection againstLeishmania majorinfection in HIV-positive patients is associated with worsened disease outcome
2015
Cutaneous leishmaniasis (CL) patients coinfected with HIV are known to show a more severe, prolonged course of disease; the immunological basis is not known. We now assessed clinical features, sera and skin biopsies of HIV(+) and HIV(-) patients with CL to identify drivers of increased susceptibility to Leishmania. CL lesion numbers, surface, and healing duration were significantly increased in HIV(+) as compared to HIV(-) patients (2.5, 14 and4-fold, respectively). Patients with HIV infection exhibited lower serum Leishmania-specific IgG levels and decreased IL-6 and IL-8. Most importantly, dramatically decreased numbers of CD4(+) T cells (approximately eightfold), but not CD8(+) cells, to…
Clinical features and epidemiology of cutaneous leishmaniasis and Leishmania major/HIV co-infection in Cameroon: results of a large cross-sectional s…
2011
Cutaneous leishmaniasis (CL) is endemic in Central Africa, including Cameroon. However, data on its prevalence and co-infection with HIV are scarce. Here we present the results of a large cross-sectional study reporting the prevalence, clinical features and species identification of CL and HIV co-infection in northern Cameroon. A total of 32 466 subjects were clinically screened for CL during a door-to-door survey, followed by parasitological diagnosis in the field laboratory. Amongst the subjects surveyed, 146 (0.4%) were diagnosed with active CL. Seven (4.8%) of these 146 CL patients tested positive for HIV-1 and/or HIV-2. The number of lesions per CL patient ranged from 1 to 20. Three of…