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Leishmania
Kinds of Leishmania Terms modified by Leishmania Selected AbstractsSignaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: Involvement of ERK1/2, NF-,B and JAK/STAT pathwaysEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2009Susanta Kar Abstract Curative effect of cystatin, a natural cystein protease inhibitor, on experimental visceral leishmaniasis was associated with strong upregulation of iNOS. The transductional mechanisms underlying this cellular response was investigated in the murine macrophage cell line RAW 264.7 and in the BALB/c mouse model of visceral leishmaniasis. Cystatin synergizes with IFN-, in inducing ERK1/2 phosphorylation and NF-,B DNA-binding activity. Pretreatment of cells with specific inhibitors of NF-,B or ERK1/2 pathway blocked the cystatin plus IFN-,-inducible NF-,B activity and markedly reduced the expression of iNOS at both mRNA and protein levels. Silencing of mitogen- and stress-activated protein kinase 1 significantly reduced cystatin-mediated NF-,B-dependent iNOS gene transcription suggesting the involvement of mitogen- and stress-activated protein kinase 1 activation in ERK1/2 signaling. DNA binding as well as silencing experiments revealed the requirement of IFN-,-mediated JAK-STAT activation even though cystatin did not modulate this signaling cascade by itself. In the in vivo situation, key steps in the activation cascade of NF-,B, including nuclear translocation of NF-,B subunits, I,B phosphorylation and I,B kinase, are all remarkably enhanced in Leishmania -infected mice by cystatin. Understanding the molecular mechanisms through which cystatin modulates macrophage effector responses will contribute to better define its potential for macrophage-associated diseases, in general. [source] A novel form of NF-,B is induced by Leishmania infection: Involvement in macrophage gene expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008David Abstract Leishmania spp. are obligate intracellular parasites that inhabit the phagolysosomes of macrophages. Manipulation of host cell signaling pathways and gene expression by Leishmania is critical for Leishmania's survival and resultant pathology. Here, we show that infection of macrophages with Leishmania promastigotes in vitro causes specific cleavage of the NF-,B p65RelA subunit. Cleavage occurs in the cytoplasm and is dependent on the Leishmania protease gp63. The resulting fragment, p35RelA, migrates to the nucleus, where it binds DNA as a heterodimer with NF-,B p50. Importantly, induction of chemokine gene expression (MIP-2/CXCL2, MCP-1/CCL2, MIP-1,/CCL3, MIP-1,/CCL4) by Leishmania is NF-,B dependent, which implies that p35RelA/p50 dimers are able to activate transcription, despite the absence of a recognized transcriptional transactivation domain. NF-,B cleavage was observed following infection with a range of pathogenic species, including L.,donovani, L.,major, L.,mexicana, and L.,(Viannia) braziliensis, but not the non-pathogenic L.,tarentolae or treatment with IFN-,. These results indicate a novel mechanism by which a pathogen can subvert a macrophage's regulatory pathways to alter NF-,B activity. [source] Intradermal NKT cell activation during DNA priming in heterologous prime-boost vaccination enhances T cell responses and protection against LeishmaniaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Blaise Dondji Abstract Heterologous prime-boost vaccination employing DNA-vaccinia virus (VACV) modality using the Leishmania homologue of receptors for activated C,kinase (LACK) (p36) antigen has been shown to elicit protective immunity against both murine cutaneous and visceral leishmaniasis. However, DNA priming is known to have limited efficacy; therefore in the current study the effect of NKT cell activation using ,-galactosyl-ceramide (,GalCer) during intradermal DNAp36 priming was examined. Vaccinated mice receiving ,GalCer,+ DNAp36 followed by a boost with VVp36 appeared to be resolving their lesions and had at ten- to 20-fold higher reductions in parasite burdens. NKT cell activation during ,GalCer,+ DNAp36 priming resulted in higher numbers of antigen-reactive effector CD4+ and CD8+ T cells producing granzyme and IFN-,, with lower levels of IL-10. Although immunodepletion studies indicate that both CD4 and CD8 T cells provide protection in the vaccinated mice, the contribution of CD4+ T cells was significantly increased in mice primed with DNAp36 together with ,GalCer. Notably 5,months after boosting, mice vaccinated with DNAp36,+ ,GalCer continued to show sustained and heightened T cell immune responses. Thus, heterologous prime-boost vaccination using ,GalCer during priming is highly protective against murine cutaneous leishmaniasis, resulting in the heightened activation and development of CD4 and CD8 T cells (effector and memory T cells). [source] Uncompromised generation of a specific H-2DM-dependent peptide-MHC class,II complex from exogenous antigen in Leishmania mexicana -infected dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003Clare Abstract Leishmania infection inhibits the capacity of macrophages (M,) to present antigens to CD4+ T cells. Relocation of MHC class,II and H-2DM to the parasitophorous vacuole (PV) and their subsequent degradation by the parasite may contribute to this defect. Dendritic cells (DC) are critical for initiation of primary T cell responses. DC can process Leishmania antigen and elicit Leishmania -specific T cells, but it is unknown whether exposure to Leishmania impairs this capacity. In particular, it is not clear whether DC containing live parasites efficiently process and present antigens. We investigated the ability of mouse bone marrow-derived DC infected with L. mexicana to generate pigeon cytochrome,c (PCC) peptide-MHC class II complexes, using the mAb D4, which recognizes PCC89,104 H-2Ek, and the PCC-specific T cell hybridoma 2B4. We show that H-2DM-dependent complex generation is not compromised by infection and that complexes are fully recognized by specific T cells. We further show that in contrast to infected M,, in infected DC cytoplasmic H-2DM is not down-regulated and not relocated to the parasite-containing vacuole. This observation may explain the continued ability of infected DC to present PCC, and also indicates differences in the habitat of these intracellular parasites in DC compared to M,. [source] Immune response to leishmania: paradox rather than paradigmFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Parul Tripathi Abstract The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. It is estimated that 350 million people are at risk, with a global yearly incidence of 1,1.5 million for cutaneous and 500 000 for visceral leishmaniasis (VL). VL is a major cause of morbidity and mortality in East Africa and the Indian subcontinent. Coinfection with HIV enhances the risk of the disease. The only control measure currently available in India is case detection and treatment with antimonial drugs, which are expensive, not always available and cannot be self-administered. Newer drugs like oral miltefosine have not become widely available. Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir. A detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection. [source] A case with two unusual findings: cutaneous leishmaniasis presenting as panniculitis and pericarditis after antimony therapyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2010Aydolu Ery, lmaz MD Background, Cutaneous leishmaniasis is a parasitic disease caused by a Protozoan. Clinically and histopathologically, it can be confused with various dermatologic diseases. Methods, We report a case of cutaneous leishmaniasis (CL) with two unusual findings. A 49-year-old male patient presented to our clinic with a 3-month history of multiple nodules exhibiting arciform arrangement on the lateral side of the left leg. Results, Histopathologic examination revealed it as nodular vasculitis. Leishmania smear showed suspicious parasites. Although leishmania culture was negative, PCR was positive for Leishmania. The patient was considered to have CL and was treated with systemic meglumine antimoniate for 14 d. Three days after the end of the treatment, the patient presented to emergency room with a sharp, pleuritic chest pain. He was diagnosed with pericarditis based on clinical and electrocardiogram findings. As other causes of pericarditis were absent, it was thought to be related to antimony therapy. Conclusion, The histopathologic presentation of CL as panniculitis is a very rare and this is the first case of pericarditis after the antimony treatment. [source] Efficacy of glucantime in the treatment of Old World cutaneous leishmaniasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2009Rukhsana Firdous MPhil Background, Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Depending on the parasite species and host response, the disease presents itself in different clinical forms. The cutaneous form of the disease is most common in the Old World. Pentavalent antimonials in the form of an injection represent the most widely used therapy for all clinical forms of the disease. As a result of reports on the development of resistance from various parts of the world, we thought it pertinent to determine its response in our region. Methods, Two hundred and seven military personnel with cutaneous leishmaniasis, caused by Leishmania major, were treated with glucantime according to the World Health Organization (WHO) recommended protocol. All patients were nonindigenous to the area and had moved from a nonendemic area to a highly endemic area. Results, Thirty-seven per cent of patients were cured within 15 days. The cure percentage reached 81% when 20 mg/kg/day was continued to 20 days. Twenty-five patients who failed to respond were subjected to a further course of glucantime injection. Sixteen responded by the 10th day of treatment, and the remaining nine were cured by completion of the second course, i.e. within 40 days. The drug was administered intramuscularly. The common side-effects noted were vertigo, headache, anorexia, temperature, and joint pain. Conclusion, Glucantime is still effective against Old World cutaneous leishmaniasis when used in the doses recommended by WHO. [source] Clinical features of cutaneous and disseminated cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in Paraty, Rio de JaneiroINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2008Ricardo Vieira-Gonçalves MD Background, American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis is endemic in Rio de Janeiro State (RJ), where the disease shows epidemiologic and clinical characteristics distinct from those of ATL in other Brazilian regions. Paraty is the second most important endemic area in RJ; however, reports on leishmaniasis in this region refer to the occurrence of the disease without describing its characteristics. Methods, The clinical features of 71 cases of ATL reported between 1991 and 1997 in Paraty are presented. Thirty patients were re-evaluated 10 years later. Results, Males and females were affected in similar proportions, and the disease was more prevalent in patients aged between 10 and 49 years (63.4%). Cutaneous leishmaniasis was the most prevalent clinical form observed. Unique lesions were present in 69% of cases, 91.6% of which displayed an ulcerated aspect. Although mucosal leishmaniasis was not observed, severe clinical manifestations, such as disseminated cutaneous lesions caused by L. braziliensis, were diagnosed in two patients. These patients presented skin lesions with different clinical aspects spread throughout the body, as well as low cellular immune responses. Montenegro skin test (92% positivity) and serology (8% IgM and 56% IgG anti- Leishmania positive results) were the most utilized tests for supporting the diagnosis of leishmaniasis. Parasites, detected in 27 of the 33 cases analyzed, were characterized as L. braziliensis. Conclusion, ATL in Paraty shares the clinical and laboratory characteristics reported for ATL in other regions of RJ, probably because of the similar epidemiologic context related to the Atlantic rainforest region. [source] Cutaneous leishmaniasis reactivation 2 years after treatment caused by systemic corticosteroids , first reportINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2007Felipe Francisco Tuon MD American tegumentary leishmaniasis (ATL), an endemic anthropozoonosis in various countries in the world, is caused by parasites of the genus Leishmania. Despite reports on ATL reactivation as a result of immunosuppression, to the best of our knowledge, this paper describes the first case of ATL reactivation in its localized form (cutaneous leishmaniasis) associated with the administration of systemic corticosteroids. The possible action of corticosteroids on the host immune response to the parasite in patients with localized cutaneous leishmaniasis is discussed. This report demonstrates the possibility of ATL reactivation in patients using corticosteroids, an observation that should be considered in individuals treated with this medication. [source] Presence of Leishmania organisms in specific and non-specific skin lesions in HIV-infected individuals with visceral leishmaniasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2002Ricardo J. Bosch MD BackgroundLeishmania coinfection is frequently seen in human immunodeficiency virus (HIV)-infected patients in endemic areas, and from time to time the protozoan is detected in cutaneous biopsies. Objective To establish the characteristics and possible ethiologic role of the presence of Leishmania in these lesions. Methods We studied 12 cutaneous biopsies with Leishmania organisms from nine HIV-infected patients (seven men and two women) with visceral leishmaniasis, diagnosed by bone marrow examination, seen over a period of 9 years. Results Based on clinical characteristics, evolution and response to anti-leishmanial treatment, cutaneous alterations were found to be related to the presence of the protozoan in six cases, whereas in the other six cases it was not considered responsible for the dermatological lesions (dermatofibroma, and lesions of psoriasis, Reiter's syndrome, bacillary angiomatosis, cryptococcosis and oral aphthae). Of note was the high prevalence of specific mucocutaneous manifestations, usually accompanied by intense pruritus, great variability, and a tendency to relapse after treatment stopped. On two occasions, detection of the protozoa in skin biopsies led to the diagnosis of a previously unsuspected visceral leishmaniasis. Conclusions Cutaneous detection of Leishmania is frequent in HIV-infected individuals with visceral leishmaniasis. Sometimes Leishmania is associated with changes attributable to other dermatological processes, and its presence does not imply a causative role. A clear relationship between the systemic process and the therapeutic response is necessary to demonstrate an ethiologic role. [source] Microtubules: dynamics, drug interaction and drug resistance in LeishmaniaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2002K. G. Jayanarayan MS (Pharm) Summary Microtubules are cytoskeletal polymers essential for the survival of all eukaryotes. These proteins are the proposed cellular targets of many anticancerous, antifungal and antihelminthic drugs. Sufficient differences exist between the microtubules of kinetoplastid parasites like Leishmania and humans to explore the selective targeting of these proteins for therapeutic purposes. This review describes the basic structure of microtubules and its dynamics in general, with specific insights into leishmanial microtubules, the salient features of microtubule,drug interactions including the specificity of certain drugs for parasitic microtubules. Chemotherapy against leishmanial parasites is failing because of the emergence of drug resistant strains. The possible mechanisms of resistance to antimicrotubule agents along with insights into the role of microtubules in mediating drug resistance in Leishmania are discussed. [source] Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of Leishmania infantumJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2010Santhosh Kannan Venkatesan Abstract Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol-redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9-aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9-aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source] Laser-capture microdissection: Applications in routine molecular dermatopathologyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2004Amir S. Yazdi Applications for PCR-based diagnostics are particularly helpful for the determination of clonality in cutaneous lymphocytic infiltrates and for detection of infectious agents, such as herpes simplex virus (HSV), varicella zoster virus (VZV), Borrelia burgdorferi, Mycobacteria, Leishmania, and Treponema pallidum. As biopsies are always composed of different cells, the cells of interest are often only a minor population. As a consequence, their specific DNA is diluted by the majority of contaminating cells. Another problem is the time- and labor-intensive DNA extraction, because usually only formalin-fixed, paraffin-embedded tissue is available, which makes molecular diagnostics a time and labor consuming, and consequently a cost-intensive procedure. To overcome these shortcomings and to eventually shorten the time to generate a result, we introduce a laser-capture microdissection (LCM)-based method for the detection of infectious agents and clonality. Only the cells of interest for the particular indication are microdissected (e.g. epidermal cells for HSV and VZV and lymphocytes for clonality analysis) and subjected to PCR amplification. Due to an accelerated DNA-extraction procedure which generates DNA in 5 h (compared to 3,4 days using conventional DNA extraction), we are able to generate a result within one working day. [source] Cutaneous sterile granulomas/pyogranulomas, leishmaniasis and mycobacterial infectionsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 11 2008D. Santoro Cutaneous "sterile" granulomas represent a group of uncommon skin disorders of unknown aetiopathogenesis. Many diseases are included in this group (for example, sterile granuloma/pyogranuloma syndrome and reactive histiocytosis). The definition of sterile is based on the exclusion of other possible aetiological agents (for example, microorganisms or foreign body). Many techniques are used to rule out a microbial aetiology including cytology, histology, immunohistochemistry and culture. However, some organisms are "fastidious" and difficult to culture or to identify with routine methods, and molecular studies are necessary. This is particularly true for mycobacteria (for example, canine leproid granuloma syndrome) and Leishmania. Recently, studies in human and veterinary medicine have proved the presence of microorganisms (mycobacteria and Leishmania) using a polymerase chain reaction technique in specimens previously diagnosed as sterile. Therefore, it is very important, with the development of new technologies, to use a multidisciplinary diagnostic approach to definitively rule out any microorganism before declaring a disease sterile. [source] Characterization of a Leishmania stage-specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulenceMOLECULAR MICROBIOLOGY, Issue 2 2010Ranadhir Dey Summary Leishmaniasis is caused by the dimorphic protozoan parasite Leishmania. Differentiation of the insect form, promastigotes, to the vertebrate form, amastigotes, and survival inside the vertebrate host accompanies a drastic metabolic shift. We describe a gene first identified in amastigotes that is essential for survival inside the host. Gene expression analysis identified a 27 kDa protein-encoding gene (Ldp27) that was more abundantly expressed in amastigotes and metacyclic promastigotes than in procyclic promastigotes. Immunofluorescence and biochemical analysis revealed that Ldp27 is a mitochondrial membrane protein. Co-immunoprecipitation using antibodies to the cytochrome c oxidase (COX) complex, present in the inner mitochondrial membrane, placed the p27 protein in the COX complex. Ldp27 gene-deleted parasites (Ldp27,/,) showed significantly less COX activity and ATP synthesis than wild type in intracellular amastigotes. Moreover, the Ldp27,/, parasites were less virulent both in human macrophages and in BALB/c mice. These results demonstrate that Ldp27 is an important component of an active COX complex enhancing oxidative phosphorylation specifically in infectious metacyclics and amastigotes and promoting parasite survival in the host. Thus, Ldp27 can be explored as a potential drug target and parasites devoid of the p27 gene could be considered as a live attenuated vaccine candidate against visceral leishmaniasis. [source] The ,-glutamylcysteine synthetase gene of Leishmania is essential and involved in response to oxidantsMOLECULAR MICROBIOLOGY, Issue 4 2009Angana Mukherjee Summary Gamma-glutamylcysteine synthetase, encoded by the GSH1 gene, is the rate-limiting enzyme in the biosynthesis of glutathione and of trypanothione in Leishmania. The importance of GSH1 was assessed by generating GSH1 null mutants in Leishmania infantum. Removal of even a single wild-type allelic copy of GSH1 invariably led to the generation of an extra copy of GSH1, maintaining two intact wild-type alleles. However, by first supplementing the parasites with a rescue plasmid, we succeeded in obtaining both a single and null chromosomal GSH1 mutants. Parasites with one intact GSH1 chromosomal allele lost the rescuing plasmid but not the double knockout, when grown in the absence of antibiotic, indicating the essentiality of the GSH1 gene in Leishmania. Heterozygous mutants with one allele-inactivated transcribed less GSH1 mRNA and synthesized less glutathione and trypanothione. These mutants were more susceptible to oxidative stresses in vitro as promastigotes and showed decreased survival inside activated macrophages producing reactive oxygen or nitrogen species. These mutants showed a significant decreased survival in the presence of antimony (SbV) compared with control cells. All phenotypes were reverted in the add-back mutant, thus proving the importance of thiols in dealing with oxidants including the action of antimonials. [source] Rafts and sphingolipid biosynthesis in the kinetoplastid parasitic protozoaMOLECULAR MICROBIOLOGY, Issue 3 2004Paul W. Denny Summary Although the concept of eukaryotic lipid rafts arouses controversy, recent biophysical studies strongly indicate that inducible, stable and relatively large rafts are a feature of activated mammalian cells. These studies allow us to consider the functional role of lipid rafts in kinetoplastid parasites, which are particularly rich in lipid-anchored surface molecules. Morphological, biochemical and genetic studies indicate that lipid rafts (and sphingolipid biosythesis) are important in the differentiation of extracellular Leishmania to mammalian-infective metacyclic promastigotes, perhaps orchestrating the clearly observable reorganization of the plasma membrane during this process that leads to an activated metacyclic primed for invasion. However, the first step in the sphingolipid biosynthetic pathway (mediated by serine palmitoyltransferase), and at least regulated, de novo sphingoid base and ceramide synthesis, are not essential for the pathogenesis of intramacrophage Leishmania amastigotes. [source] The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma bruceiMOLECULAR MICROBIOLOGY, Issue 2 2003N. S. Alsford Summary Nuclear extrachromosomal DNA elements have been identified in several kinetoplastids such as Leishmania and Trypanosoma cruzi, but never in Trypanosoma brucei. They can occur naturally or arise spontaneously as the result of sublethal drug exposure of parasites. In most cases, they are represented as circular elements and are mitotically unstable. In this study we describe the presence of circular DNA in the nucleus of Trypanosoma brucei. This novel type of DNA was termed NR-element (NlaIII repeat element). In contrast to drug-induced episomes in other kinetoplastids, the T. brucei extrachromosomal NR-element is not generated by drug selection. Furthermore, the element is stable during mitosis over many generations. Restriction analysis of tagged NR-element DNA, unusual migration patterns during pulsed field gel electrophoresis (PFGE) and CsCl/ethidium bromide equilibrium centrifugation demonstrates that the NR-element represents circular DNA. Whereas it has been found in all field isolates of the parasites we analysed, it is not detectable in some laboratory strains notably the genome reference strain 927. The DNA sequence of this element is related to a 29 bp repeat present in the subtelomeric region of VSG-bearing chromosomes of T. brucei. It has been suggested that this subtelomeric region is part of a transition zone on chromosomes separating the relatively stable telomeric repeats from the recombinationaly active region downstream of VSG genes. Therefore, we discuss a functional connection between the occurrence of this circular DNA and subtelomeric recombination events in T. brucei. [source] Oral leishmaniasis in a HIV-positive patient.ORAL DISEASES, Issue 1 2002Report of a case involving the palate Leishmaniasis is a parasitic disease caused by a protozoon (Leishmania), with different clinical forms that are endemic in certain countries. The association of this disease in patients who are seropositive to human immunodeficiency virus (HIV) has recently been described. Leishmaniasis can develop in any stage of HIV infection, although the clinical manifestations , and hence the diagnosis , tend to coincide with the periods of maximum immune depression. We present the case of a HIV-positive, ex-intravenous drug abuser (in stage B2 of the CDC, 1992) with concomitant hepatitis C infection who presented with palatinal pain and bleeding for the past 2 months. Exploration revealed a vegetating tumoration of the hard palate. Hematoxylin-eosin and Giemsa staining of the biopsy confirmed the diagnosis of leishmaniasis. The definitive diagnosis was mucocutaneous leishmaniasis (MCL), for a bone marrow aspirate proved negative, and no further lesions could be established. The patient was treated with meglumine antimoniate (Glucantime), followed by improvement of the lesions. [source] A quantitative and morphometric study of mast cells in cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 11-12 2008F. F. TUON SUMMARY Background,Mast cells (MCs) are related with healing process in chronic inflammatory diseases, although in cutaneous leishmaniasis (CL) its importance is unknown. The aim of this study was to determine the correlation of MC with clinical findings in patients with the localized form of CL. Methods,A cohort of 85 patients with CL was evaluated. MCs count was performed in pre-treatment biopsies and correlation with clinical findings and Leishmania species determined by PCR were performed. Results,The MCs count in patients with CL caused by Leishmania (V.) braziliensis was 14·3 ± 9·8 cells/mm2, and 7·0 ± 6·5 cells/mm2 in patients with L. (L.) amazonensis (P < 0·05). The linear regression of MCs count with the age showed a tendency of cell number decreasing, according to ageing of the patient (r2 = 0·05; P < 0·05). The association of disease's duration and MCs count was positive (r2 = 0·11; P < 0·05). There was not any association of MCs count with number of lesions neither with Leishmania antigen expression. The MCs count was higher in patients with earlier healing after treatment (P < 0·05). Conclusion,MC can be important in CL and related with healing lesion. [source] Inflammation and structural changes of splenic lymphoid tissue in visceral leishmaniasis: A study on naturally infected dogsPARASITE IMMUNOLOGY, Issue 10 2008C. C. SANTANA SUMMARY The aim of this study was to identify splenic immuno-inflammatory patterns associated with natural infection by Leishmania chagasi. Spleen samples were obtained from 72 stray dogs from an endemic area of visceral leishmaniasis. The animals were grouped into four categories as follows: (i) potentially resistant to visceral leishmaniasis, with a positive leishmanin skin test result, and negative splenic culture for Leishmania parasites (ii) potentially susceptible to visceral leishmaniasis, with a negative leishmanin skin test and positive splenic culture for Leishmania (iii) infected with undefined susceptibility status, with a positive leishmanin skin test and positive splenic culture for Leishmania, and (iv) noninfected, with a negative leishmanin skin test, negative splenic culture for Leishmania, and negative serology for anti- Leishmania antibodies. Histopathological analyses showed that there was a higher frequency of perisplenitis (18/25, P < 0·0001), granuloma (7/25, P = 0·0102), structural disorganization (14/25, P < 0·0001), and atrophy of the lymphoid follicles (20/25, P = 0·0036) and of the marginal zone (15/25, P = 0·0025) in the potentially susceptible group than in the other groups. The data presented here show changes in the white pulp of the spleen that are associated with naturally acquired visceral leishmaniasis. [source] Expression of helminth genes in Leishmania: an experimental transfection system to test immunological functionPARASITE IMMUNOLOGY, Issue 4 2008R. M. MAIZELS SUMMARY Functional analysis of genes from parasitic helminths requires, at the present time, heterologous expression. We have adapted the well-characterized system of transfection in Leishmania protozoal parasites, as a means of analysing the effect of single filarial genes on the mammalian immune system. For example, testing the function of the Brugia malayi abundant larval transcript (ALT) gene-transfected Leishmania mexicana were found to be significantly more virulent in macrophages in vitro. The course of infection in vivo is also aggravated by expression of the ALT gene. Examples are also given of transgenes which reduced in vitro growth within macrophages, as well as others which exert no effect on the protozoal parasitism. Thus, Leishmania transfection provides a tractable system to analyse helminth gene function within the context of the host immune system. [source] Endemically exposed asymptomatic individuals show no increase in the specific Leishmania (Viannia) panamensis -Th1 immune response in comparison to patients with localized cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 9-10 2002C. M. Trujillo SUMMARY In Colombia, most cases of human cutaneous leishmaniasis are caused by Leishmania (Viannia) panamensis. Interestingly, up to 30% of the exposed population do not suffer from clinical leishmaniasis although it is likely that they are continuously infected with Leishmania parasites. Since it is believed that the induction of efficient Th1 immune responses protects against Leishmania infections both in humans and in animal models, we determined if endemically exposed asymptomatics showed stronger Leishmania -specific Th1 immune responses than patients with active localized cutaneous leishmaniasis (LCL). We found that Montenegro skin test responses were slightly higher among asymptomatic individuals compared to patients suffering from LCL. However, PBMC from patients with LCL showed similar Leishmania -specific proliferative responses compared to PBMC from asymptomatic individuals. Furthermore, PBMC from both groups also secreted similar amounts of IFN-,, IL-12p40 and IL-10 after in vitro exposure to L. panamensis. No IL-4 was detected in the supernatants. Taken together our results suggest that lack of LCL development in endemically exposed asymptomatics cannot be explained by stronger systemic anti- Leishmania Th1 immune responses or decreased Th2 responses in these individuals in comparison to individuals who develop LCL. It may be possible that other mechanisms are responsible for resistance to cutaneous leishmaniasis in Colombia in endemically exposed asymptomatics. [source] Leishmania donovani -induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesisPARASITE IMMUNOLOGY, Issue 4 2001Claudine Matte Prostaglandin E2 (PGE2) secretion during Leishmania infection has been reported. However, the signalling mechanisms mediating this response are not well understood. Since cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) are involved in PGE2 synthesis in response to various stimuli, the implication of these enzymes was evaluated in Leishmania -infected phorbol myristate acetate-differentiated U937 human monocytic cell line. Time-course experiments showed that PGE2 synthesis increased significantly in parallel with COX-2 expression when cells were incubated in the presence of Leishmania donovani promastigotes or lipopolysaccharides (LPS). Increase in cPLA2 mRNA expression was only detected when cells were stimulated with LPS. Indomethacin, genistein, and H7, which are antagonists of COX-2, protein tyrosine kinase (PTK) and protein kinase C (PKC), respectively, inhibited PGE2 production induced by L. donovani and LPS. However, only H7 inhibited COX-2 mRNA synthesis, and there was a significant correlation between PGE2 inhibition and reduced COX-2 expression. Collectively, our results indicate that infection of U937 by L. donovani leads to the generation of PGE2 in part through a PKC-dependent signalling pathway involving COX-2 expression. They further reveal that PTK-dependent events are necessary for Leishmania -induced PGE2 generation, but not for COX-2 expression. A better understanding of the mechanisms by which Leishmania can induce PGE2 production could provide insight into the pathophysiology of leishmaniasis and may help to improve therapeutic approaches. [source] Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1-like response in American cutaneous leishmaniasis patientsPARASITE IMMUNOLOGY, Issue 2 2000Maira Cabrera Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)-, and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL-5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN-, responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN-, responses to BCG. Treatment enhanced the IFN-, response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN-, responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL-5 levels. There were no significant changes in serum IL-5 with treatment. Overall results show enhanced antigen-specific IFN-, responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN-,. [source] In vitro Leishmanicidal activity of naturally occurring chalconesPHYTOTHERAPY RESEARCH, Issue 2 2001Oliver Kayser Abstract A variety of chalcones have been shown to exhibit activity against Leishmania parasites. In contrast to synthetic or semisynthetic chalcones, only a few plant-derived compounds have been investigated. To provide a scientific rational for the antiprotozoal potency of plants used in ethnomedicine and containing chalcones, and in the search for new antiprotozoal drugs, we have carried out a primary screening for in vitro leishmanicidal activity of 20 chalcones isolated from plants. The compounds were tested against extracellular promastigotes of Leishmania donovani, L. infantum, L. enrietii and L. major, and against intracellular amastigote L. donovani residing within murine macrophages. Against the extracellular Leishmania (L. donovani), most compounds were active with EC50 values between 0.07 and 2.01,µg/mL. Some of these chalcones, 2,,4,-dihydroxy-4-methoxychalcone, 2,-hydroxy-3,4-dimethoxychalcone and 2-hydroxy-4,4,-dimethoxychalcone also significantly inhibited the intracellular survival of L. donovani parasites with EC50 values between 0.39 and 0.41,µg/mL. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, all compounds with antileishmanial activities also proved to be cytotoxic to varying extents (EC50 0.19,2.06,µg/mL). Correlations between molecular structures and antileishmanial activity are discussed in detail. Specific compounds are illustrated with emphasis on their mode of action and potential for the development of selective antiprotozoal agents. Copyright © 2001 John Wiley & Sons, Ltd. [source] A combined proteomic and transcriptomic approach to the study of stage differentiation in Leishmania infantumPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2006François McNicoll Abstract Protozoan parasites of the genus Leishmania are found as promastigotes in the sandfly vector and as amastigotes in mammalian macrophages. Mechanisms controlling stage-regulated gene expression in these organisms are poorly understood. Here, we applied a comprehensive approach consisting of protein prefractionation, global proteomics and targeted DNA microarray analysis to the study of stage differentiation in Leishmania. By excluding some abundant structural proteins and reducing complexity, we detected and identified numerous novel differentially expressed protein isoforms in L.,infantum. Using 2-D gels, over 2200,protein isoforms were visualized in each developmental stage. Of these, 6.1% were strongly increased or appeared unique in the promastigote stage, while the relative amounts of 12.4% were increased in amastigotes. Amastigote-specific protein isoform and mRNA expression trends correlated modestly (53%), while no correlation was found for promastigote-specific spots. Even where direction of regulation was similar, fold-changes were more modest at the RNA than protein level. Many proteins were present in multiple spots, suggesting that PTM is extensive in this organism. In several cases, different isoforms appeared to be specific to different life stages. Our results suggest that post-transcriptional controls at translational and post-translational levels could play major roles in differentiation in Leishmania parasites. [source] The structure and domain organization of Escherichia coli isocitrate lyaseACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2001K. L. Britton Enzymes of the glyoxylate-bypass pathway are potential targets for the control of many human diseases caused by such pathogens as Mycobacteria and Leishmania. Isocitrate lyase catalyses the first committed step in this pathway and the structure of this tetrameric enzyme from Escherichia coli has been determined at 2.1,Å resolution. E. coli isocitrate lyase, like the enzyme from other prokaryotes, is located in the cytoplasm, whereas in plants, protozoa, algae and fungi this enzyme is found localized in glyoxysomes. Comparison of the structure of the prokaryotic isocitrate lyase with that from the eukaryote Aspergillus nidulans reveals a different domain structure following the deletion of approximately 100 residues from the larger eukaryotic enzyme. Despite this, the active sites of the prokaryotic and eukaryotic enzymes are very closely related, including the apparent disorder of two equivalent segments of the protein that are known to be involved in a conformational change as part of the enzyme's catalytic cycle. [source] Kaposi's sarcoma-like lesions and other nodules as cutaneous involvement in AIDS-related visceral leishmaniasisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2000M.J. González-Beato A 40-year-old human immunodeficiency virus (HIV)-positive man had three relapses of visceral leishmaniasis (VL). In the third he developed nodular skin lesions of three types, some reminiscent of Kaposi's sarcoma. Biopsy of each type disclosed abundant dermal macrophages with a huge number of intracellular and extracellular Leishman,Donovan bodies. Rapid improvement of lesions was achieved after antiparasitic treatment. AIDS leads to atypical forms of leishmaniasis. Leishmania has been detected both in normal and pathological skin of these patients due to dissemination during VL. It is suspected that a considerable proportion of the population may be infected in endemic areas, Leishmania being opportunistic in immunosuppressed individuals. It is important to recognize the range of lesions that may occur in patients with HIV and VL, many of which are non-specific and may cause diagnostic difficulty. [source] Leishmania cell surface prohibitin: role in host,parasite interactionCELLULAR MICROBIOLOGY, Issue 4 2010Rohit Jain Summary Proteins selectively upregulated in infective parasitic forms could be critical for disease pathogenesis. A mammalian prohibitin orthologue is upregulated in infective metacyclic promastigotes of Leishmania donovani, a parasite that causes visceral leishmaniasis. Leishmania donovani prohibitin shares 41% similarity with mammalian prohibitin and 95,100% within the genus. Prohibitin is concentrated at the surface of the flagellar and the aflagellar pole, the aflagellar pole being a region through which host,parasite interactions occur. Prohibitin is attached to the membrane through a GPI anchor. Overexpression of wild-type prohibitin increases protein surface density resulting in parasites with higher infectivity. However, parasites overexpressing a mutant prohibitin with an amino acid substitution at the GPI anchor site to prevent surface expression through GPI-link show lesser surface expression and lower infective abilities. Furthermore, the presence of anti-prohibitin antibodies during macrophage,Leishmania interaction in vitro reduces infection. The cognate binding partner for Leishmania prohibitin on the host cell appears to be macrophage surface HSP70, siRNA mediated downregulation of which abrogates the capability of the macrophage to bind to parasites. Leishmania prohibitin is able to generate a strong humoral response in visceral leishmaniasis patients. The above observations suggest that prohibitin plays an important role in events leading to Leishmania,host interaction. [source] | ||||||||||||||||||||||||||||||||||