Search results for " Leishmaniasis"

Cutaneous leishmaniasis: Distinct functions of dendritic cells and macrophages in the interaction of the host immune system with Leishmania major

2017

Leishmaniasis is transmitted by sand flies leading to parasite inoculation into skin. In the mammalian host, the parasite primarily resides in skin macrophages (MΦ) and dendritic cells (DC). MΦ are silently invaded by the parasite eliciting a stress response, whereas DC become activated, release IL-12, and prime antigen-specific T cells. Here we review the basics of the immune response against this human pathogen and elucidate the role and function DC and MΦ for establishment of protective immunity against leishmaniasis. We focus on cell type-specific differences in parasite uptake, phagocyte activation and processing of parasite antigens to facilitate an understanding how their respective …

Interleukin 1α Promotes Th1 Differentiation and Inhibits Disease Progression in Leishmania major–susceptible BALB/c Mice

2003

Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12–dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1α in response to lipopolysaccharide/interferon γ or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1α mRNA accumulation in l…

Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE

2018

Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…

Requirements for Th1-dependent immunity against infection with Leishmania major

2004

Protective immunity against cutaneous leishmaniasis is dependent on the induction of Th1/Tc1 immune responses resulting in efficient parasite elimination. In this review, the mechanisms leading to protection are discussed with special focus on the role of Leishmania major-infected dendritic cells (DC) in induction of Th1-dependent immunity. Murine strain-dependent differences between DC derived from Leishmania-susceptible as compared to resistant mice are highlighted.

Advances in leishmaniasis immunopathogenesis

2011

Suspected cutaneous leishmaniasis in a sample of Western Sicily residents: what correlation with occupation?

2017

Background: Leishmaniasis is a widespread infectious disease, but there is not much information about its prevalence in high risk occupational categories. Objectives: Te aim of this study is to assess the prevalence of Leishmania immunological positivity in human skin tissues collected from subjects living in Western Sicily, with suspected cutaneous Leishmania infection, in order to explore the risk possibly related to occupation. Methods: 318 consecutive subjects (M/F ratio=1.0, mean age=40±25.4 years), attending the Dermatology Department of the University of Palermo Hospital from 2013 to 2015, without any previous history of Leishmania infection and performing various occupations, were i…

Decreased presence of Langerhans cells is a critical determinant for Indian Post kala-azar dermal leishmaniasis.

2015

Post kala-azar dermal leishmaniasis (PKDL) is the dermal sequel of visceral leishmaniasis (VL) and occurs after apparent cure or alongside with VL. It is confined to South Asia (India, Nepal and Bangladesh) and East Africa (mainly Sudan), the incidence being 5-10% and 50-60% respectively. In South Asia, as the transmission of VL is anthroponotic, PKDL patients are the proposed disease reservoir, thus assuming epidemiological significance, its eradication being linked to the control of leishmaniasis. In the absence of an animal model and its low incidence, factors contributing towards the immunopathogenesis of PKDL remain an open-ended, yet pertinent question. This study delineated the lesio…

Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to visceral leishmani…

2019

Abstract Visceral leishmaniasis (VL) is a parasitic disease that is endemic in more than 80 countries, and leads to high fatality rates when left untreated. We investigate the relationship of VL cases in dogs and human cases, specifically for evidence of VL in dogs leading to excess cases in humans. We use surveillance data for dogs and humans for the years 2007–2011 to conduct both spatial and spatio-temporal analyses. Several models are evaluated incorporating varying levels of dependency between dog and human data. Models including dog data show marginal improvement over models without; however, for a subset of spatial units with ample data, models provide concordant risk classification …

Hemophagocytic Lymphohistiocytosis in Early Infancy- Pitfall of Differentiation between Hereditary and Infectious Reasons

2018

Abstract Hemophagocytic Lymphohistiocytosis (HLH) is characterized by pathologic immune activation which occurs either as a familial disorder or as an acquired condition. The diagnosis of HLH requires the presence of five out of nine criteria: fever, splenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis in bone marrow, hyperferritinemia, low or absent natural killer cell activity and high level of soluble interleukin-2 receptor. Here we present a 6-month-old girl with parents from Southern Italy. She suffered from hepatosplenomegaly and a recurrent high fever for 3 months' duration. On admission, she showed neurological symptoms including irritability and ne…

Polymerase chain reaction in the diagnosis and prognosis of Mediterranean visceral leishmaniasis in immunocompetent children.

2002

Objective. To assess the usefulness of a polymerase chain reaction (PCR) assay amplifying the small subunit rRNA coding region of Leishmania species performed on peripheral blood (PB) and bone marrow (BM) aspirates for the diagnosis and follow-up of visceral leishmaniasis (VL) in children living in the Mediterranean basin. Design. A prospective study was conducted on children consecutively hospitalized over a 1-year period at our Infectious Diseases Department in Sicily (Italy) presenting with fever, hepatosplenomegaly, and/or pancytopenia and a positive Leishmania serology (≥1:40). Results. Among the 14 patients hospitalized with signs and symptoms suggestive of the disease and a positive …