Search results for "Leishmaniasis"
showing 10 items of 148 documents
Humanized mice in cutaneous leishmaniasis—Suitability analysis of human PBMC transfer into immunodeficient mice
2019
Humanized mice represent a suitable preclinical test system for example therapeutic interventions in various disease settings, including infections. Here, we intended to establish such system for cutaneous leishmaniasis by infecting T, B and NK cell-deficient mice adoptively transferred with human peripheral blood mononuclear cells (PBMC). L major infection led to the establishment of parasite lesions harbouring viable parasites and human T cells, but parasite elimination was not seen due to a species-specific activity of T cell-derived human IFNγ. In addition, up to 50% of infected mice succumbed to severe graft-versus-host disease. In summary, even though long-term disease outcome assessm…
A case of visceral leishmaniasis and pulmonary tuberculosis in a post-partum woman
2015
AbstractVisceral leishmaniasis due to Leishmania infantum is a vector-borne zoonotic disease transmitted by sand fly bites endemic in rural or periurban areas of the Mediterranean basin. Pregnancy is accompanied by changes in immune response, mainly a decrease in cellular immunity and a proportional increase in humoral immunity. These physiological events result in increased risk of infection by pathogens whose immunity is based on a T-helper 1 predominant response. We describe a case of visceral leishmaniasis and pulmonary tuberculosis diagnosed in a post-partum woman four days after delivery. The diagnosis of leishmaniasis should be considered in pregnant women with fever and haematologic…
Keratinocytes Determine Th1 Immunity during Early Experimental Leishmaniasis
2010
Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediat…
Nivolumab Enhances In Vitro Effector Functions of PD-1+ T-Lymphocytes and Leishmania-Infected Human Myeloid Cells in a Host Cell-Dependent Manner
2017
Functional impairment of T-cells and a concomitant augmented expression of programmed death-1 (PD-1) have been observed in visceral leishmaniasis patients, as well as in experimental models for visceral and cutaneous leishmaniasis. The PD-1/PD-1-ligand (PD-1/PD-L) interaction negatively regulates T-cell effector functions, which are required for parasite control during leishmaniasis. The aim of this study was to elucidate the impact of the PD-1/PD-L axis in a human primary in vitro infection model of Leishmania major (Lm). Blocking the PD-1/PD-L interaction with nivolumab increased T-cell proliferation and release of the proinflammatory cytokines TNFα and IFNγ during the cocultivation of Lm…
Discovery of benzimidazole-based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis
2018
Abstract: Chemotherapy is currently the only effective approach to treat all forms of leishmaniasis. However, its effectiveness is severely limited due to high toxicity, long treatment length, drug resistance, or inadequate mode of administration. As a consequence, there is a need to identify new molecular scaffolds and targets as potential therapeutics for the treatment of this disease. We report a small series of 1,2‐substituted‐1H‐benzo[d]imidazole derivatives (9ad) showing affinity in the submicromolar range (Ki = 0.150.69 μM) toward Leishmania mexicanaCPB2.8ΔCTE, one of the more promising targets for antileishmanial drug design. The compounds confirmed activity in vitro against intrace…
The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis
2020
Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…
Treatment options for leishmaniasis.
2021
Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.
Focused ultrasound to diagnose HIV-associated tuberculosis (FASH) in the extremely resource-limited setting of South Sudan: a cross-sectional study
2019
ObjectiveOur cross-sectional study aimed at evaluating the diagnostic performance of Focused Assessment with Sonography for HIV-associated tuberculosis (FASH) to detect extrapulmonary tuberculosis in extremely resource-limited settings, with visceral leishmaniasis as a differential diagnosis with overlapping sonographic feature.DesignCross-sectional study.SettingVoluntary Counselling and Testing Centre (VCT) of Yirol Hospital, South Sudan.ParticipantsFrom May to November 2017, 252 HIV-positive patients out of 624 newly admitted to VCT Centre were registered for antiretroviral treatment. According to the number of trained doctors available to practise ultrasound (US) scan, a sample of 100 pa…
Oral leishmaniasis in an HIV-infected patient.
2000
As in most countries in the Mediterranean basin, leishmaniasis is endemic in Italy, where it has visceral (VL) and cutaneous (CL) forms caused by viscerotropic and dermotropic strains of Leishmania infantum, respectively. With the spread of the acquired immunodeficiency syndrome (AIDS) epidemic, the number of coinfections with Leishmania and human immunodeficiency virus (HIV) is increasing. Between 35% and 50% of the adult VL cases diagnosed annually in Sicily from 1991 to 1995 were related to HIV [1]; although cases of coinfection have been reported in 28 countries worldwide, the majority of these cases (1440 from 1990 to 1998) have been notified in four countries (Spain, Italy, France, Po…