Disease relevance of Leishmania

• By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes [1].
• Prior exposure of mice to bites of uninfected sand flies conferred powerful protection against Leishmania major that was associated with a strong delayed-type hypersensitivity response and with interferon-gamma production at the site of parasite delivery [2].
• In keeping with recent data (13-15), where strong cross protection among different Leishmania species has been obtained by prophylactic immunization with irradiated whole promastigotes, this glycoprotein may be a good candidate for an antigen to be used for immunoprophylaxis of all forms of Leishmaniasis [3].
• Natural resistance to infection with unrelated intracellular parasites such as Mycobacteria, Salmonella, and Leishmania is controlled in the mouse by a single gene on chromosome 1, designated Bcg, Ity, or Lsh [4].
• In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates [5].

Psychiatry related information on Leishmania

• It has been hypothesized that the Leishmania use a system of camouflage or mimicry of human ABO blood group antigens to evade host defense mechanisms [6].

High impact information on Leishmania

• (2004) describe the identification of an insect galectin as the receptor for the stage-specific Leishmania adhesin lipophosphoglycan (LPG) [7].
• Methotrexate-resistant Leishmania tropica contain two separate regions of DNA amplification, one encoding the bifunctional thymidylate synthetase-dihydrofolate reductase (TS-DHFR) characteristic of protozoans and the other of yet unknown function [8].
• Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization [8].
• RNA has been isolated from highly purified kinetoplast-mitochondrial fractions of Leishmania tarentolae, and shown to consist of two major species that sediment at 9S and 12S in sucrose and also several additional low molecular weight species which were visualized by gel electrophoresis [9].
• These data uncover a new immune evasion strategy, whereby Leishmania differentially modulates CD40-engaged, reciprocally functioning signaling modules, and provide a new conceptual framework for immune homeostasis [10].

Chemical compound and disease context of Leishmania

• Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock [11].
• DATA SYNTHESIS: Nodular lymphangitis develops most commonly after cutaneous inoculation with Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, Leishmania braziliensis, and Francisella tularensis [12].
• Formycin B is cytotoxic toward Leishmania and is a potential chemotherapeutic agent for leishmaniasis [13].
• Neither wild type nor MTXA5 cells could multiply in folate-deficient medium, and thymine and thymidine at concentrations which circumvented methotrexate toxicity, did not restore the ability of Leishmania to grow [14].
• BALB/c mice were injected in the footpad with Leishmania tropica, NIH S-strain; in mice that were not pretreated with BCG this produced a reproducible fatal infection characterized by local inflammation, regional lymphadenopathy, and dissemination of parasites with hepatosplenomegaly [15].

Biological context of Leishmania

• Control of tubulin gene expression in the parasitic protozoan Leishmania enriettii [16].
• The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major [17].
• Northern blot analyses indicated that the Ld peptide/gene is broadly distributed and expressed among species of the Leishmania genus, in both the amastigote and promastigote life cycle forms [18].
• Cloning and expression of a Leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class II molecules of infected macrophages [18].
• CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation [19].

Anatomical context of Leishmania

• Paradoxically, IL-10, another CD40-induced cytokine in macrophages, promotes Leishmania infection [10].
• The opsonized promastigotes undergo an immune adherence reaction and bind quantitatively to erythrocyte CR1 receptors; opsonized Leishmania amastigotes also bind to erythrocytes [20].
• Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine [21].
• Monocytes produced neither IL-1 nor TNF-alpha during challenge with Leishmania [22].
• We showed that early endosome fusion in Leishmania is temperature and cytosol dependent and is inhibited by ATP depletion, ATPgammaS, GTPgammaS and N-ethylmaleimide treatment [23].

Associations of Leishmania with chemical compounds

• We now describe the stable expression of a selectable marker, the gene for neomycin resistance (neor) in Leishmania enriettii [24].
• We report here results which suggest that in Leishmania promastigotes there are either distinct EHNA-sensitive dyneins or different conformational states of a single dynein involved in the cilia-like and flagella-like waveforms and in the propagation of flagellar waves from tip-to-base and from base-to-tip [25].
• The dinitroaniline herbicide trifluralin (alpha, alpha, alpha-trifluoro-2,6-dinitro-N, N-dipropyl-p-toluidine), at micromolar concentrations, selectively inhibited both proliferation and differentiation of the parasitic protozoan Leishmania mexicana amazonensis [26].
• Lethal effect of phenothiazine neuroleptics on the pathogenic protozoan Leishmania donovani [27].
• Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells [28].

Gene context of Leishmania

• Susceptibility to leishmaniasis is controlled by multiple genes [29].
• Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection was established [30].

• Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection [31].
• Despite mounting a vigorous interferon-gamma response, HS IV-deficient mice were more susceptible to Leishmania major infection than were wild-type littermate control mice, showing a critical function for Il4 silencing in T helper type 1-mediated immunity [32].
• CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major [33].
• Interleukin 10 production correlates with pathology in human Leishmania donovani infections [34].
• Cells preinfected with Leishmania synthesized normal amounts of TNF-alpha, but had diminished production of IL-1 in response to stimulation with either S. aureus or lipopolysaccharide (LPS) [22].

Analytical, diagnostic and therapeutic context of Leishmania

• Effective immunotherapy was achieved with CCR7-expressing DCs, without the need to identify protective Leishmania antigens [35].
• Enzymatic surface iodination and biosynthetic labeling with [35S]methionine, combined with immunoprecipitation by sera from patients with different forms of Leishmaniasis revealed a 65,000 Mr glycoprotein as the immunodominant moiety in promastigotes and amastigotes of the nine Leishmania species and isolates examined [3].
• Molecular cloning and characterization of the immunologically protective surface glycoprotein GP46/M-2 of Leishmania amazonensis [36].
• Database mining and sequence analysis identified putative glyoxalase I genes in the eukaryotic human parasites Leishmania major, Leishmania infantum, and Trypanosoma cruzi, with highest similarity to the cyanobacterial enzymes [37].
• We generated Leishmania lacking PTR1 by homologous gene targeting, and these ptr1- mutants required reduced biopterin (dihydro- or tetrahydrobiopterin) for growth [38].

References