Publications

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antiprotozoal activity of (e)-cinnamic n-acylhydrazone derivatives.a series of 14 (e)-cinnamic n-acylhydrazone derivatives, designed through molecular hybridization between the (e)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)prop-2-en-1-one and (e)-3-hydroxy-n'-((2-hydroxynaphthalen-1-yl)methylene)-7-methoxy-2-naphthohydrazide, were tested for in vitro antiparasitic activity upon axenic amastigote forms of leishmania donovani and bloodstream forms of trypamosoma brucei rhodesiense. the derivative (2e)-3-(4-hydroxy-3-methoxy-5-nitrophenyl)-n'-[(1e)-phenylmethy ...201425490429
leishmania donovani infection enhances lateral mobility of macrophage membrane protein which is reversed by liposomal cholesterol.the protozoan parasite leishmania donovani (ld) reduces cellular cholesterol of the host possibly for its own benefit. cholesterol is mostly present in the specialized compartment of the plasma membrane. the relation between mobility of membrane proteins and cholesterol depletion from membrane continues to be an important issue. the notion that leishmania infection alters the mobility of membrane proteins stems from our previous study where we showed that the distance between subunits of ifnγ re ...201425474261
role of cd8(+) t cells in protection against leishmania donovani infection in healed visceral leishmaniasis individuals.majority of individuals with history of visceral leishmaniasis (vl) exhibit strong immunity to re-infection, however, the mechanism of resistance is poorly understood. it is unclear whether cd8(+) t cells contribute to protection against leishmania donovani infection through cytotoxic activity. the present study aims to evaluate immunological mechanism associated with resistance to the disease in healed vl (hvl) individuals and further, the contribution of cd8(+) t cells in the protective immuni ...201425471494
genes that encodes nagt, mif1 and mif2 are not virulence factors for kala-azar caused by leishmania infantum.kala-azar is a disease resulting from infection by leishmania donovani and leishmania infantum. most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. however, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. among the parasite molecules that might influence the disease severity are the macrophage migration inhibitory fact ...201425467261
pkdl and other dermal lesions in hiv co-infected patients with leishmaniasis: review of clinical presentation in relation to immune responses.co-infection of leishmaniasis and hiv is increasingly reported. the clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by hiv-induced immunosuppression. as leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (pkdl) and cutaneous leishmaniasis (cl); dermal lesions are also commonly reported in visc ...201425412435
leishmania donovani populations in eastern sudan: temporal structuring and a link between human and canine transmission.visceral leishmaniasis (vl), caused by the members of the leishmania donovani complex, has been responsible for devastating vl epidemics in the sudan. multilocus microsatellite and sequence typing studies can provide valuable insights into the molecular epidemiology of leishmaniasis, when applied at local scales. here we present population genetic data for a large panel of strains and clones collected in endemic sudan between 1993 and 2001.201425410888
analysis of genetic variants in the il4 promoter and vntr loci in indian patients with visceral leishmaniasis.visceral leishmaniasis (vl) is the most severest form of leishmaniasis and resistance to infection is mediated by cellular immune responses. interleukin 4 (il-4) orchestrates of th2 and th1 immune responses during infections. in this study, we aimed to investigate possible association between three functional il-4 polymorphisms -590c/t (rs2243250), -34c/t (rs2070874) and 70bp vntr (rs79071878 in intron3) with vl in an indian cohort comprising of 197 vl patients and 193 healthy controls. the thre ...201425454624
bioactive derivatives of isopropylstilbene from mutasynthesis and chemical synthesis.isopropylstilbene is a natural product from photorhabdus luminescens tt01, with multiple biological activities. a mutant deficient in the production of both anthraquinones and cinnamic acid was constructed, thus giving a clean background according to uv detection. this anthraquinone and stilbene deficient (asd) mutant was used in mutasynthesis experiments to obtain new stilbene derivatives, which were detected by gc-ms. the structures of the new derivatives were confirmed by detailed ms analysis ...201425346446
a cluster of four cases of cutaneous leishmaniasis by leishmania donovani in cyprus: a case series.leishmaniasis is endemic in more than 95 countries and is the only tropical/subtropical vector-borne disease that has been endemic in southern europe for decades. to the best of our knowledge, this is the first case of cutaneous leishmaniasis by leishmania donovani in a child and the first cluster with adult cases reported in europe.201425343876
igg1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test.visceral leishmaniasis (vl), caused by protozoa of the leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic vl is usually fatal. distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.201425340782
pharmacological activities of cilantro's aliphatic aldehydes against leishmania donovani.leishmaniasis is a chronic infectious disease caused by different leishmania species. global occurrences of this disease are primarily limited to tropical and subtropical regions. treatments are available; however, patients complain of side effects. different species of plants have been screened as a potential source of new drugs against leishmaniasis. in this study, we investigated the antileishmanial activity of cilantro (coriandrum sativum) essential oil and its main components: (e)-2-undecen ...201425340465
regulation of pkc mediated signaling by calcium during visceral leishmaniasis.calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various ca2+ pumps and channels. two such fundamental calcium pumps are plasma membrane calcium atpase (pmca) and sarco/endoplasmic reticulum calcium atpase (serca) which play a pivotal role in maintaining intracellular calcium homeostasis. this intracellular ca2+ homeostasis is often disturbed by the protozoan parasite ...201425329062
the treatment of visceral leishmaniasis: safety and efficacy.visceral leishmaniasis is the disease of poor; however availability of only expensive treatment of this disease impinges the socioeconomic condition of those affected. if untreated, almost all cases of visceral leishmaniasis are fatal. the demonstration of the leishmania donovani bodies from the tissue aspirates or serological tests confirms the diagnosis of the disease. pentavalent antimony, amphotericin b, paromomycin, diamine pentamidine, miltefosine, sitamaquine and some new combinations are ...201425327244
leishmania donovani infection causes distinct epigenetic dna methylation changes in host macrophages.infection of macrophages by the intracellular protozoan leishmania leads to down-regulation of a number of macrophage innate host defense mechanisms, thereby allowing parasite survival and replication. the underlying molecular mechanisms involved remain largely unknown. in this study, we assessed epigenetic changes in macrophage dna methylation in response to infection with l. donovani as a possible mechanism for leishmania driven deactivation of host defense. we quantified and detected genome-w ...201425299267
new series of monoamidoxime derivatives displaying versatile antiparasitic activity.following the promising antileishmanial results previously obtained in monoamidoxime series, a new series of derivatives was synthesized using manganese(iii) acetate, wittig reactions and suzuki-miyaura cross coupling reactions. pharmacomodulation in r(1), r(2) or r(3) substituents on the amidoxime structure is shown to influence antiprotozoan activity in vitro: a monosubstituted phenyl group in r1 (32-35) led to an activity against leishmania donovani promastigotes (32, ic50 = 9.16 μm), whereas ...201425282267
comparative proteomics and glycoproteomics of plasma proteins in indian visceral leishmaniasis.visceral leishmaniasis (vl) is a deadly parasitic diseases caused by leishmania donovani; it is a major health problem in many countries. a lack of proper understanding of the disease biology, poor diagnostic methods and increasing drug resistance are the main reasons for the growing burden of vl infection. comparative plasma proteomics are a relatively useful technique that can be used to investigate disease-associated alterations that can help in understanding host responses against pathogens, ...201425276097
th1 stimulatory proteins of leishmania donovani: comparative cellular and protective responses of rtriose phosphate isomerase, rprotein disulfide isomerase and relongation factor-2 in combination with rhsp70 against visceral leishmaniasis.in visceral leishmaniasis, the recovery from the disease is always associated with the generation of th1-type of cellular responses. based on this, we have previously identified several th1-stimulatory proteins of leishmania donovani -triose phosphate isomerase (tpi), protein disulfide isomerase (pdi) and elongation factor-2 (el-2) etc. including heat shock protein 70 (hsp70) which induced th1-type of cellular responses in both cured leishmania patients/hamsters. since, hsps, being the logical t ...201425268700
a bioinformatics approach to reanalyze the genome annotation of kinetoplastid protozoan parasite leishmania donovani.leishmania donovani is a kinetoplastid protozoan parasite which causes the fatal disease visceral leishmaniasis in humans. genome sequencing of l. donovani revealed information about the arrangement of genes and genome architecture. after curation of the genome sequence, many genes in l. donovani were assigned as truncated or "partial" genes by the genome sequencing group. in the present study, we have carried out an extensive analysis and attempted to improve the gene models of these partial ge ...201425265881
new flavonol methyl ether from the leaves of vitex peduncularis exhibits potential inhibitory activity against leishmania donovani through activation of inos expression.one new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of vitex peduncularis wall and three known compounds from the leaves of methanol extract of vitex pinnata linn (verbenaceae) were isolated. the chemical structure of the new compound was established by detailed spectroscopic studies. the in vitro antileishmanial activities of 1 against both leishmania donovani promastigote and amastigote forms were evaluated. to characterize the effector mechan ...201425264585
quinone-amino acid conjugates targeting leishmania amino acid transporters.the aim of the present study was to investigate the feasibility of targeting leishmania transporters via appropriately designed chemical probes. leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (ldaap3 and ldaap7) to import these nutrients. probes 1-15 were originated by conjugating cytotoxic quinone fragments (ii and iii) with amino acids (i.e. arginine and lysine) by means of an amide linkage. the toxicit ...201425254495
the antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors.histone deacetylase inhibitors (hdaci) pleiotropy is largely due to their nonselective inhibition of various cellular hdac isoforms. connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting hdaci pleiotropy. the contribution of classes i and ii hdacs to the antileishmanial activity of hdaci was investigated using the amastigote and promastigote forms of leishmania donovani. we observed that the antileishmanial activities of hdaci are ...201425240614
novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents.we have previously shown that 3-nitro-1h-1,2,4-triazole-based arylamides and arylsulfonamides demonstrate significant activity in vitro against trypanosoma cruzi, the causative parasite of chagas disease. more importantly, several such analogs displayed significant antichagasic activity in vivo, superior to that of benznidazole, the current clinical standard. we now report the synthesis and in vitro evaluation of a small series of novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamid ...201425240098
structure-based design of potent and selective leishmania n-myristoyltransferase inhibitors.inhibitors of leishmania n-myristoyltransferase (nmt), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. crystal structures bound to leishmania major nmt were obtained, and the active diastereoisomer of one of the inhibitors was identified. on the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent leishmani ...201425238611
an imported case of cutaneous leishmaniasis caused by leishmania (leishmania) donovani in japan.leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. there have been few reports of leishmaniasis in japan and all were of foreign origin; therefore diagnosis is difficult for japanese physicians. there are 21 different pathogenic leishmania species, and identification is obtained by polymerase chain reaction (pcr). here we report an imported case of leishmaniasis by leishmania (leishmania) donovani infection from sri lanka. l. (l.) d ...201425228325
tlr mediated gsk3β activation suppresses creb mediated il-10 production to induce a protective immune response against murine visceral leishmaniasis.during leishmania donovani (ld) infection interleukin (il)-10 favors parasite replication and plays a central role as a target for immune-based therapy. glycogen synthase kinase 3 (gsk3)β differentially regulates tlr-mediated cytokine production. creb, an important transcription factor that induces il-10 production is negatively regulated by gsk3β. however, down regulation of il-10 via creb suppression has not been well explored in controlling ld infection. here we demonstrate that, the tlr4 ago ...201425223889
leishmania donovani activates srebp2 to modulate macrophage membrane cholesterol and mitochondrial oxidants for establishment of infection.establishment of infection by an intracellular pathogen depends on successful internalization with a concomitant neutralization of host defense machinery. leishmania donovani, an intramacrophage pathogen, targets host srebp2, a critical transcription factor, to regulate macrophage plasma membrane cholesterol and mitochondrial reactive oxygen species generation, favoring parasite invasion and persistence. leishmania infection triggered membrane-raft reorientation-dependent lyn-pi3k/akt pathway ac ...201425218172
imipramine exploits histone deacetylase 11 to increase the il-12/il-10 ratio in macrophages infected with antimony-resistant leishmania donovani and clears organ parasites in experimental infection.the efflux of antimony through multidrug resistance protein (mdr)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant leishmania donovani (sb(r)ld). previously we showed that mdr-1 upregulation in sb(r)ld infection is il-10-dependent. imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits il-10 production from sb(r)ld-infected macrophages (sb(r)ld-mϕs) and favors accumulation of surrogate ...201425217162
insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in leishmania donovani.leishmaniasis is a parasitic disease caused by the protozoan leishmania, which is active in two broad forms namely, visceral leishmaniasis (vl or kala azar) and cutaneous leishmaniasis (cl). the disease is most prevalent in the tropical regions and poses a threat to over 70 countries across the globe. about 200 million people are estimated to be at risk of developing vl in the indian subcontinent, and this refers to around 67% of the global vl disease burden. the indian state of bihar alone acco ...201425206363
sitamaquine-resistance in leishmania donovani affects drug accumulation and lipid metabolism.this study focuses on the mechanism of sitamaquine-resistance in leishmania donovani. sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (wt) and of sitamaquine-resistant (sita-r160) l. donovani promastigotes, respectively. the sitamaquine accumulation was a concentration-dependent process in wt whereas a saturation occurred in sita-r160 suggesting a reduced uptake or an increase of the sitamaquine efflux. membrane negative phospholipids being the main target ...201425201056
immunotherapy and targeted therapies in treatment of visceral leishmaniasis: current status and future prospects.visceral leishmaniasis (vl) is a vector-borne chronic infectious disease caused by the protozoan parasite leishmania donovani or leishmania infantum. vl is a serious public health problem, causing high morbidity and mortality in the developing world with an estimated 0.2-0.4 million new cases each year. in the absence of a vaccine, chemotherapy remains the favored option for disease control, but is limited by a narrow therapeutic index, significant toxicities, and frequently acquired resistance. ...201425183962
a small heat shock protein is essential for thermotolerance and intracellular survival of leishmania donovani.leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. the change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. although the functions of the main heat shock protein fami ...201425179594
comparison of pcr with stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis.visceral leishmaniasis (vl), also known as kala-azar, is a disseminated protozoan infection caused by leishmania donovani complex. traditionally the definite diagnosis is made by amastigote detection in the tissue. the aim this study was to evaluate the pcr technique in stained slides of bone marrow and lymph nodes aspirates with suspect diagnosis for leishmaniasis. slides were selected totaling 62 suspect cases (33 bone marrow samples and 29 lymph node samples) and 17 positive cases (8 bone mar ...201425159534
characterization of cross-protection by genetically modified live-attenuated leishmania donovani parasites against leishmania mexicana.previously, we showed that genetically modified live-attenuated leishmania donovani parasite cell lines (ldcen(-/-) and ldp27(-/-)) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. in this study, we explored the mechanism of cross-protection against cutaneous lesion-causing leishmania mexicana. upon challenge with wild-type l. mexicana, mice immunized either for short or long periods showed significant protection. immunohistochemical analysis of ea ...201425156362
combining cationic liposomal delivery with mpl-tdm for cysteine protease cocktail vaccination against leishmania donovani: evidence for antigen synergy and protection.with the paucity of new drugs and hiv co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (vl) requiring strong cellular immunity. protein vaccination often suffers from low immunogenicity and poor generation of memory t cells for long-lasting protection. cysteine proteases (cps) are immunogenic proteins and key mediators of cellular functions in leishmania. here, we evaluated the vaccine efficacies of cps against vl, using cationic liposomes with toll l ...201425144181
in vitro anti-leishmanial efficacy of potato tuber extract (ptex): leishmanial serine protease(s) as putative target.leishmaniasis, a neglected tropical disease (ntd) causes major health problems in the tropical and subtropical world. most of the antileishmanial modern therapies with different formulations of pentavalent antimonials, miltefosine, amphotericin b etc. are not satisfactory in recent times due to high toxicity to the host and present rising strain resistance issues. so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. in this regard, bioactive phytocompon ...201425128800
ascorbate peroxidase, a key molecule regulating amphotericin b resistance in clinical isolates of leishmania donovani.amphotericin b (amb), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in india. amb relapse cases and the emergence of secondary resistance have now been reported. to understand the mechanism of amb, differentially expressed genes in amb resistance strains were identified by a dna microarray and real-time reverse transcriptase pcr (rt-pcr) approach. of the many genes functionally overexpressed in the presence of amb, the ascorbate pero ...201425114128
characterization of mitochondrial bioenergetic functions between two forms of leishmania donovani - a comparative analysis.leishmaniasis is a growing health problem in many parts of the world partly due to drug resistance of the parasite. this study reports on the fisibility of studying mitochondrial properties of two forms of wild-type l. donovani through the use of selective inhibitors. amastigote forms of l. donovani exhibited a wide range of sensitivities to these inhibitors. mitochondrial complex ii inhibitor thenoyltrifluoroacetone and fof1-atp synthase inhibitors oligomycin and dicyclohexylcarbodiimide were r ...201425107348
a screen-and-treat strategy targeting visceral leishmaniasis in hiv-infected individuals in endemic east african countries: the way forward?in the wake of the hiv epidemic, visceral leishmaniasis (vl), a disseminated protozoan infection caused by the leishmania donovani complex, has been re-emerging, particularly in north ethiopia where up to 40% of patients with vl are co-infected with hiv. management of vl in hiv co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. tackling l. donovani infection befor ...201425101627
a new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies.artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity.201425086720
carbon nanotube based betulin formulation shows better efficacy against leishmania parasite.we report a novel antileishmanial formulation of betulin (bet) attached to functionalized carbon nanotubes (f-cnts). we conjugated betulin, a pentacyclic triterpenoid secondary metabolite, to carboxylic acid chains on f-cnts to obtain bet attached functionalized carbon nanotubes (f-cnt-bet). the drug release profile demonstrated a fairly slow release of bet. the in-vitro cytotoxicities of bet, f-cnt and f-cnt-bet on j774a.1 macrophage cell line were 211.05±7.14μg/ml; 24.67±3.11μg/ml and 72.63±6. ...201425086374
protection against experimental visceral leishmaniasis by immunostimulation with herbal drugs derived from withania somnifera and asparagus racemosus.visceral leishmaniasis (vl) is a vector-borne parasitic disease targeting tissue macrophages. it is among the most neglected infectious diseases. as available therapeutics for treatment of this disease have many side effects, there is a need for safer alternatives. one of the immunopathological consequences of active visceral leishmaniasis is suppression of protective t-helper (th)-1 cells and induction of disease-promoting th-2 cells, and thus the treatment of vl relies on immunomodulation. in ...201425082945
diverse modes of binding in structures of leishmania major n-myristoyltransferase with selective inhibitors.the leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. it is therefore widely accepted that new therapies are needed. n-myristoyltransferase (nmt) has been validated pre-clinically as a target for the treatment ...201425075346
induction of mitochondrial dysfunction and oxidative stress in leishmania donovani by orally active clerodane diterpene.this study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (k-09) in leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (vl). k-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in l. donovani promastigotes. mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the ...201425070112
reactive oxygen species regulates expression of iron-sulfur cluster assembly protein iscs of leishmania donovani.the cysteine desulfurase, iscs, is a highly conserved and essential component of the mitochondrial iron-sulfur cluster (isc) system that serves as a sulfur donor for fe-s clusters biogenesis. fe-s clusters are versatile and labile cofactors of proteins that orchestrate a wide array of essential metabolic processes, such as energy generation and ribosome biogenesis. however, no information regarding the role of iscs or its regulation is available in leishmania, an evolving pathogen model with rap ...201425062827
isolated cutaneous leishmaniasis by leishmania donovani in a soldier returning from afghanistan. 201525062262
reduction of leishmania donovani infectivity in whole blood using riboflavin and ultraviolet light.leishmaniasis is a vector-borne disease caused by the protozoan parasite leishmania sp. that is transmitted by sandflies. travelers to endemic areas, and us military personnel stationed in the middle east, are at risk for contracting the disease.201525156473
leishmania donovani phosphoproteins pp41 and pp29 re-establishes host protective immune response in visceral leishmaniasis.as phospho proteins are reported to be involved in virulence and survival, the ability of leishmania to inhibit macrophage effector functions may result from a direct interference of leishmanial molecules with macrophage signal transduction pathways. several such proteins such as pp63, pp41 and pp29 have also been identified as a th1 stimulatory protein in the leishmania donovani. in the present study, the immunogenicity of a cocktail of pp63+pp41+pp29 was assessed by estimation of serum antibod ...201525224164
evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis.despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. recent research has documented that efforts to develop effective leishmania vaccine have been limited due to the lack of an appropriate adjuvant. addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. so, the present study was done to evaluate the effectiven ...201525316605
granzyme-mediated regulation of host defense in the liver in experimental leishmania donovani infection.in the livers of susceptible c57bl/6 (b6) mice infected with leishmania donovani, cd8(+) t cell mechanisms are required for granuloma assembly, macrophage activation, intracellular parasite killing, and self-cure. since gene expression of perforin and granzymes a and b (gzma and gzmb), cytolytic proteins linked to cd8(+) cell effector function, was enhanced in infected liver tissue, b6 mice deficient in these granular proteins were used to gauge host defense roles. neither perforin nor gzma was ...201525452549
leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of leishmania in visceral leishmaniasis.ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, t(sh)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in visceral leishmaniasis. data on the relationship between ornithine decarboxylase and the cellular immune response in vl patients are limited. therefore, we purified a recombinant ornithine decarboxylase from leishmania donovani (r-ldodc) of appro ...201525449949
evaluation of the immunogenicity and protective efficacy of killed leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis.visceral leishmaniasis (vl) caused by leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. a safe and efficacious vaccine to control this disease is needed. killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity ...201525432859
anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from tibouchina paratropica.a new phenolic derivative, 2,8-dihydroxy-7h-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of tibouchina paratropica. compound structures were elucidated by spectroscopic methods. both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against leishmania donovani (ic50  = 0.809 µg/ml). in addition, an 85% reduction in the secretion of the pro-inflammato ...201525417600
specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis.acute visceral leishmaniasis (vl) is caused by infection with parasites of the leishmania donovani complex and may be fatal if not treated. early diagnosis and efficacious treatment are the keys to effective vl management and control. novel regimens are being developed to overcome limitations in vl treatment options, which are currently restricted by high costs, severe systemic side effects, and unresponsiveness. although simple and accurate serological tests are available to help confirm vl, no ...201525407374
nitroimidazo-oxazole compound dndi-vl-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis.the objective of this study was to identify a nitroimidazo-oxazole lead molecule for the treatment of visceral leishmaniasis (vl).201525389223
screening leishmania donovani complex-specific genes required for visceral disease.leishmania protozoan parasites are the causing agent of leishmaniasis. depending on the infecting species, leishmania infection can causes a wide variety of diseases such as self-healing cutaneous lesions by l. major and fatal visceral leishmaniasis by l. donovani and l. infantum. comparison of the visceral disease causing l. infantum genome with cutaneous disease causing l. major and l. braziliensis genomes has identified 25 l. infantum (l. donovani complex) species-specific genes that are abse ...201525388124
characterization of microrna expression profiles in leishmania-infected human phagocytes.leishmania are intracellular protozoa that influence host immune responses eliciting parasite species-specific pathologies. micrornas (mirnas) are short single-stranded ribonucleic acids that complement gene transcripts to block protein translation and have been shown to regulate immune system molecular mechanisms. human monocyte-derived dendritic cells (dc) and macrophages (mp) were infected in vitro with leishmania major or leishmania donovani parasites. small rnas were isolated from total rna ...201525376316
identification of leishmania donovani peroxin 14 residues required for binding the peroxin 5 receptor proteins.trafficking of peroxisomal targeting signal 1 (pts1) proteins to the leishmania glycosome is dependent on the docking of the ldpex5 receptor to ldpex14 on the glycosomal membrane. a combination of deletion and random mutagenesis was used to identify residues in the ldpex14 n-terminal region that are critical for mediating the ldpex5-ldpex14 interaction. these studies highlighted residues 35-75 on ldpex14 as the core domain required for binding ldpex5. single point mutation within this core domai ...201525370715
cationic liposomal sodium stibogluconate (ssg), a potent therapeutic tool for treatment of infection by ssg-sensitive and -resistant leishmania donovani.pentavalent antimonials have been the first-line treatment for leishmaniasis for decades. however, the development of resistance to sodium stibogluconate (ssg) has limited its use, especially for treating visceral leishmaniasis (vl). the present work aims to optimize a cationic liposomal formulation of ssg for the treatment of both ssg-sensitive (ag83) and ssg-resistant (ge1f8r and ck1r) leishmania donovani infections. parasite killing was determined by the 3-(4,5-dimethylthiazol-2)-2,5-diphenyl ...201525367907
design, synthesis and anti-leishmanial activity of novel symmetrical bispyridinium cyclophanes.nine novel symmetrical bispyridinium cyclophanes have been synthesized. they are rigid derivatives with an upper spacer which joins the two exocyclic amino groups, and a lower spacer joining the two positively charged nitrogen atoms. at least one of the two spacers is an aliphatic linker, such as an alkane or oxyalkane fragment. the activity of these compounds has been evaluated against promastigotes and intracellular amastigotes of leishmania donovani and leishmania major. all the cyclophanes a ...201525462252
unmethylated cpg motifs in the l. donovani dna regulate tlr9-dependent delay of programmed cell death in macrophages.regulation of macrophage pcd plays an important role in pathogenesis of leishmaniasis. however, the precise involvement of any parasite molecule in this process remains uncertain. in the current study, in silico wide analysis demonstrated that genes in the leishmania donovani genome are highly enriched for cpg motifs, with sequence frequency of 8.7%. here, we show that unmethylated species-specific cpg motifs in lddna significantly (p = 0.01) delay macrophage pcd by endosomal interaction with tl ...201525473100
characterization of a ricin-resistant mutant of leishmania donovani that expresses lipophosphoglycan.the abundant cell-surface lipophosphoglycan (lpg) of leishmania parasites plays a central role throughout the eukaryote's life cycle. a number of lpg-defective mutants and their complementing genes have been isolated and have proven invaluable in assessing the importance of lpg and related glycoconjugates in parasite virulence. while ricin agglutination selection protocols frequently result in lpg- mutants, one  leishmania donovani variant we isolated, named jabba, was found to be lpg+. procycli ...201525472443
mechanisms of action of substituted β-amino alkanols on leishmania donovani.leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. under this perspective, a quest for new chemical compounds is urgently needed. an n-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. knowledge about its mechanism of action is still rather limited. in this work, we endea ...201525487805
cutaneous leishmaniasis caused by leishmania donovani in the tribal population of the agasthyamala biosphere reserve forest, western ghats, kerala, india.cutaneous leishmaniasis (cl), a neglected tropical disease, is reported to be prevalent in tribal villages located in the agasthyamala biosphere reserve forests of western ghats, kerala state, india. we carried out an investigation to characterize the species of leishmania parasites involved in these infections prevalent among one of the oldest human tribal populations in india. skin aspirates collected from 13 clinically diagnosed cases were subjected to histopathological investigations, serolo ...201525480880
a defective oxidative burst and impaired antigen presentation are hallmarks of human visceral leishmaniasis.survival of the leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (vl).201525479930
vaccination using live attenuated leishmania donovani centrin deleted parasites induces protection in dogs against leishmania infantum.live attenuated leishmania donovani parasites such as ldcen(-/-) have been shown elicit protective immunity against leishmanial infection in mice and hamster models. previously, we have reported on the induction of strong immunogenicity in dogs upon vaccination with ldcen(-/-) including an increase in immunoglobulin isotypes, higher lymphoproliferative response, higher frequencies of activated cd4(+) and cd8(+) t cells, ifn-γ production by cd8(+) t cells, increased secretion of tnf-α and il-12/i ...201525475955
chemotherapy of leishmaniasis part xiii: design and synthesis of novel heteroretinoid-bisbenzylidine ketone hybrids as antileishmanial agents.some novel heteroretinoid-bisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of leishmania donovani. among all the nine synthetic compounds, five compounds (7c, 7d and 7f-h) have shown significant (less than 7μm) activity against intramacrophagic amastigotes. the ic50 values of these compounds were found better than the reference drugs sodium stibogluconate (ssg) and miltefosine. this study helped us ...201525475205
arg-265: a critical residue of l.donovani cytosolic shmt in maintaining the binding of thf and catalysis.serine hydroxymethyltransferase belongs to the class of pyridoxal-5-phosphate enzymes along with aspartate aminotransferase. to explore the function of residue(s) involved in binding of the carboxylate group of tetrahydrofolic acid (thf) to l. donovani cytosolic serine hydroxymethyltransferase (ldcshmt), the gene was cloned in pet-28(a) vector, overexpressed and purified to homogeneity. with the help of docking results of thf to the active site of protein, the key residues involved in interactio ...201525499510
design, synthesis and in vitro antikinetoplastid evaluation of n-acylated putrescine, spermidine and spermine derivatives.a structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. among them, a spermidine derivative (compound 13) was specifically active in vitro against leishmania donovani axenic amastigotes (ic50 at 5.4μm; selectivity index >18.5) and a spermine derivative (compound 28) specifically active against trypanosoma brucei gambiense (ic50 at 1.9μm; selectivity index >52).201525499437
immunological consequences of stress-related proteins--cytosolic tryparedoxin peroxidase and chaperonin tcp20--identified in splenic amastigotes of leishmania donovani as th1 stimulatory, in experimental visceral leishmaniasis.in earlier studies, proteomic characterization of splenic amastigote fractions from clinical isolates of leishmania donovani, exhibiting significant cellular responses in cured leishmania subjects, led to the identification of cytosolic tryparedoxin peroxidase (ldctryp) and chaperonin-tcp20 (ldtcp20) as th1-stimulatory proteins. both the proteins, particularly ldtcp20 for the first time, were successfully cloned, overexpressed, purified and were found to be localized in the cytosol of purified s ...201525498563
novel protein-protein interaction between spermidine synthase and s-adenosylmethionine decarboxylase from leishmania donovani.polyamine biosynthesis pathway has long been considered an essential drug target for trypanosomatids including leishmania. s-adenosylmethionine decarboxylase (adometdc) and spermidine synthase (spdsyn) are enzymes of this pathway that catalyze successive steps, with the product of the former, decarboxylated s-adenosylmethionine (dcsam), acting as an aminopropyl donor for the latter enzyme. here we have explored the possibility of and identified the protein-protein interaction between spdsyn and ...201525511700
randomized, double-blind, controlled, comparative study on intralesional 10% and 15% hypertonic saline versus intralesional sodium stibogluconate in leishmania donovani cutaneous leishmaniasis.intralesional 7% hypertonic saline (hs) has been shown to be effective and safe against leishmania donovani and leishmania major cutaneous leishmaniasis (cl), with cure rates of 92% and 96%, respectively. this study was designed to assess the efficacy and safety of 10% and 15% hs in cl.201525600472
selective elimination of leptomonas from the in vitro co-culture with leishmania.leishmania and leptomonas are protozoan parasites of the family trypanosomatidae. leishmania donovani causes the fatal visceral leishmaniasis (vl; kala-azar) in mammals and is transmitted by sand fly vector. certain vl-cured human populations in india and sudan develop post kala-azar dermal leishmaniasis (pkdl) due to the same parasite. although leptomonas is parasitic mainly in insects, several recent reports on the clinical isolates of l. donovani from vl and pkdl patients in india confirm co- ...201525582929
th1-biased immunomodulation and therapeutic potential of artemisia annua in murine visceral leishmaniasis.in the absence of vaccines and limitations of currently available chemotherapy, development of safe and efficacious drugs is urgently needed for visceral leishmaniasis (vl) that is fatal, if left untreated. earlier we reported in vitro apoptotic antileishmanial activity of n-hexane fractions of artemisia annua leaves (aal) and seeds (aas) against leishmania donovani. in the present study, we investigated the immunostimulatory and therapeutic efficacy of aal and aas.201525568967
anti-citrullinated peptide antibodies in sudanese patients with leishmania donovani infection exhibit reactivity not dependent on citrullination.african patients with leishmania donovani infections have signs of strong systemic inflammation and high levels of circulating immune complexes (ic) and rheumatoid factor (rf), all serologic markers of rheumatic disease. as inflammation in general is associated with citrullination, we sought to investigate acpa responses in sudanese leishmania patients. serum samples were collected from sudanese patients with visceral leishmaniasis (vl) and post-kala-azar dermal leishmaniasis (pkdl) as well as f ...201525565324
looking for new antileishmanial derivatives in 8-nitroquinolin-2(1h)-one series.from a recently identified antileishmanial pharmacophore, a structure-activity relationship study was conducted by introducing various aminated, phenoxy or thiophenoxy moieties at position 4 of the 8-nitroquinolin-2(1h)-one scaffold, using snar reactions. thus a series of 47 derivatives was synthesized and evaluated in vitro on the promastigote stage of leishmania donovani. in parallel, the cytotoxicity of the active molecules was tested on the human hepg2 cell line. the results we obtained show ...201525559208
mucocutaneous leishmaniasis caused by leishmania donovani infection in an indian man.leishmaniasis is a protozoal disease caused by species of leishmania. mucocutaneous leishmaniasis (mcl) involves the skin and mucosa. india is endemic for species such as leishmania donovani and leishmania major, which are responsible for visceral and cutaneous leishmaniasis, respectively. although mcl has been reported from india previously, the implicated pathogen was identified as l. donovani in only one case.201525557311
adaptation of leishmania donovani to cutaneous and visceral environments: in vivo selection and proteomic analysis.leishmaniasis is a neglected tropical disease caused by leishmania protozoa. two main forms are found in the old world, self-limited cutaneous leishmaniasis and potentially fatal visceral leishmaniasis, with parasite dissemination to liver, bone marrow, and spleen. the leishmania donovani species complex is the causative agent of visceral leishmaniasis worldwide, but atypical l. donovani strains can cause cutaneous leishmaniasis. we hypothesized that l. donovani can adapt to survive in response ...201525536015
therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced t cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.visceral leishmaniasis (vl) or kala-azar (ka) is one of the most deadly forms of disease among all neglected tropical diseases. there are no satisfactory drugs or vaccine candidates available for this dreaded disease. our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (i.m.) and intraperitoneal (i.p.) route in balb/c mice model.201525532783
leishmanial sphingolipid induces apoptosis in sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover.sphingolipids are membrane and intracellular lipids that typically modulate cellular processes to cause cell death. exogenous administration of sphingolipids may cause restriction of tumour growth and several alternative strategies are being used to control the cell growth. the microbes, their cellular component(s) or metabolites like dha, epa and also fty720 have been employed as new therapeutic entities to regulate the disease condition. the therapeutic efficacy of lipids from leishmania donov ...201525524576
"squalenoylcurcumin" nanoassemblies as water-dispersible drug candidates with antileishmanial activity.curcumin, a natural polyphenolic compound, showed antiparasitic potential, including trypanocidal and leishmanicidal activity, in several in vitro and in vivo models. the molecule is well tolerated in humans. however, it is insoluble in water and displays poor oral bioavailability as a result of low absorption. new derivatives of curcumin were prepared by esterification of one or two of its phenolic groups with 1,1',2-tris-norsqualenic acid. these "squalenoylcurcumins" were formulated as water-d ...201525523035
detection of leishmania donovani and l. tropica in ethiopian wild rodents.human visceral (vl, also known as kala-azar) and cutaneous (cl) leishmaniasis are important infectious diseases affecting countries in east africa that remain endemic in several regions of ethiopia. the transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various leishmania spp., sand fly vectors, and reservoir animals besides human hosts. particularly in east africa, the role of animals as reservoirs for human vl remai ...201525700710
leishmania donovani skews the cd56(+) natural killer t cell response during human visceral leishmaniasis.the objective of this study was to understand the categorical function of cd4(+)cd56(+) and cd8(+)cd56(+) nkt cells in human visceral leishmaniasis. these cell populations were significantly deregulated in human peripheral blood during vl. the in vitro experiments showed that cd4(+)nkt cells, but not cd8(+)nkt cells, migrated towards the leishmania donovani infection site. additionally, cd4(+)nkt cells from vl subjects primarily expressed cd25(+)foxp3 and il-10 compared with healthy subjects. ho ...201525697139
metabolic reconfiguration of the central glucose metabolism: a crucial strategy of leishmania donovani for its survival during oxidative stress.understanding the mechanism that allows the intracellular protozoan parasite leishmania donovani (ld) to respond to reactive oxygen species (ros) is of increasing therapeutic importance because of the continuing resistance toward antileishmanial drugs and for determining the illusive survival strategy of these parasites. a shift in primary carbon metabolism is the fastest response to oxidative stress. a (14)co2 evolution study, expression of glucose transporters together with consumption assays, ...201525690656
repurposing of the open access malaria box for kinetoplastid diseases identifies novel active scaffolds against trypanosomatids.phenotypic screening had successfully been used for hit generation, especially in the field of neglected diseases, in which feeding the drug pipeline with new chemotypes remains a constant challenge. here, we catalyze drug discovery research using a publicly available screening tool to boost drug discovery. the malaria box, assembled by the medicines for malaria venture, is a structurally diverse set of 200 druglike and 200 probelike compounds distilled from more than 20,000 antimalarial hits fr ...201525690568
proteomic-based approach to gain insight into reprogramming of thp-1 cells exposed to leishmania donovani over an early temporal window.leishmania donovani, a protozoan parasite, is the causative agent of visceral leishmaniasis. it lives and multiplies within the harsh environment of macrophages. in order to investigate how intracellular parasite manipulate the host cell environment, we undertook a quantitative proteomic study of human monocyte-derived macrophages (thp-1) following infection with l. donovani. we used the isobaric tags for relative and absolute quantification (itraq) method and liquid chromatography-tandem mass s ...201525690103
antigen presenting cells targeting and stimulation potential of lipoteichoic acid functionalized lipo-polymerosome: a chemo-immunotherapeutic approach against intracellular infectious disease.antigen presenting cells (apc) are well-recognized therapeutic targets for intracellular infectious diseases, including visceral leishmaniasis. these targets have raised concerns regarding their potential for drug delivery due to overexpression of a variety of receptors for pathogen associated molecular pathways after infection. since, lipoteichoic acid (lta), a surface glycolipid of gram-positive bacteria responsible for recognition of bacteria by apc receptors that also regulate their activati ...201525671728
up-regulation of silent information regulator 2 (sir2) is associated with amphotericin b resistance in clinical isolates of leishmania donovani.silent information regulator 2 (sir2) is involved in parasite survival and apoptosis. here, we aimed to explore the involvement of sir2 in amphotericin b (amb) resistance mechanism in leishmania donovani.201525667407
the host-protective effect of arabinosylated lipoarabinomannan against leishmania donovani infection is associated with restoration of ifn-γ responsiveness.visceral leishmaniasis (vl), which is endemic as a major infectious disease in the tropical and subtropical countries, is caused by a protozoan parasite leishmania donovani. at present, restricted treatment options and lack of vaccines intensify the problem of controlling vl. therefore, finding a novel immunoprophylactic or therapeutic principle is a pressing need. here, we report that arabinosylated lipoarabinomannan (ara-lam), a tlr2-ligand isolated from mycobacterium smegmatis, exhibits a str ...201525658110
protective effect of croton caudatus geisel leaf extract against experimental visceral leishmaniasis induces proinflammatory cytokines in vitro and in vivo.in the present state of overwhelming emergence of drug-unresponsive phenotypes of leishmania donovani and persistent severe toxicity in conventional anti-leishmanial therapy, in search for novel leads, the aim of this study has been fixed to identify the active extract(s) of croton caudatus geisel. var. tomentosus hook effective against the parasitic protozoans in vitro and in vivo. c. caudatus geisel. is often used by chakma and hmar community, the local tribes of north-east india for medicinal ...201525655407
surface-engineered dendrimeric nanoconjugates for macrophage-targeted delivery of amphotericin b: formulation development and in vitro and in vivo evaluation.the present study aimed to develop an optimized dendrimeric delivery system for amphotericin b (amb). fifth-generation (5.0 g) poly(propylene imine) (ppi) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including fourier transform infrared spectroscopy (ftir), (1)h nuclear magnetic resonance ((1)h-nmr) spectroscopic analysis, and atomic force microscopy (afm). mannose-conjugated 5.0 g ppi (mppi) dendrimers were loaded with amb and ...201525645852
experimental resistance to drug combinations in leishmania donovani: metabolic and phenotypic adaptations.together with vector control, chemotherapy is an essential tool for the control of visceral leishmaniasis (vl), but its efficacy is jeopardized by growing resistance and treatment failure against first-line drugs. to delay the emergence of resistance, the use of drug combinations of existing antileishmanial agents has been tested systematically in clinical trials for the treatment of visceral leishmaniasis (vl). in vitro, leishmania donovani promastigotes are able to develop experimental resista ...201525645828
antiprotozoal activity and dna binding of dicationic acridones.dicationic acridone derivatives were synthesized and their antiparasitic activity was evaluated. acridones displayed in vitro nanomolar ic50 values against trypanosoma brucei rhodesiense stib900 with selectivity indices >1000. compounds 1b, 3a, and 3b were as potent as the reference drug melarsoprol in this assay. submicromolar-range activities were observed against wild-type (nf54) and resistant (k1) strains of plasmodium falciparum, whereas no significant activity was detected against trypanos ...201525642604
northalrugosidine is a bisbenzyltetrahydroisoquinoline alkaloid from thalictrum alpinum with in vivo antileishmanial activity.screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from thalictrum alpinum. a spectroscopic study of the active compounds was conducted to confirm their identities. of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against leishmania donovani promastigotes (0.28 μm) and the highest selectivity (29.3-fold) versus ...201525629555
synthesis and biological evaluation of ferrocenylquinoline as a potential antileishmanial agent.the emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against leishmania donovani. 7-chloro-n-[2-(1h-5-ferrocenyl-1,2,3-triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(ii) ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click chemistry. the synthesized compo ...201525619822
studies on cocktails of 31-kda, 36-kda and 51-kda antigens of leishmania donovani along with saponin against murine visceral leishmaniasis.a substantial number of antigens of leishmania donovani have been described in the past. however, identifying candidate antigens is not enough. appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen-specific th1 type of immune response) is another crucial component of an effective vaccine. therefore, 'cocktail' vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. studies have bee ...201525615543
leishmania infantum amastigotes trigger a subpopulation of human b cells with an immunoregulatory phenotype.visceral leishmaniasis is caused by the protozoan parasites leishmania infantum and leishmania donovani. this infection is characterized by an uncontrolled parasitization of internal organs which, when left untreated, leads to death. disease progression is linked with the type of immune response generated and a strong correlation was found between disease progression and serum levels of the immunosuppressive cytokine il-10. other studies have suggested a role for b cells in the pathology of this ...201525710789
the neurotrophic receptor ntrk2 directs lymphoid tissue neovascularization during leishmania donovani infection.the neurotrophic tyrosine kinase receptor type 2 (ntrk2, also known as trkb) and its ligands brain derived neurotrophic factor (bdnf), neurotrophin-4 (nt-4/5), and neurotrophin-3 (nt-3) are known primarily for their multiple effects on neuronal differentiation and survival. here, we provide evidence that ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. we show that in leishmania donovani-infected mice, ntrk2 is aberrantly expressed on splenic endo ...201525710496
antimony-resistant leishmania donovani exploits mir-466i to deactivate host myd88 for regulating il-10/il-12 levels during early hours of infection.infection with antimony-resistant leishmania donovani (sb(r)ld) induces aggressive pathology in the mammalian hosts as compared with ones with antimony-sensitive l. donovani (sb(s)ld) infection. sb(r)ld, but not sb(s)ld, interacts with tlr2/tlr6 to induce il-10 by exploiting p50/c-rel subunits of nf-κb in infected macrophages (mϕs). most of the tlrs exploit the universal adaptor protein myd88 to activate nf-κb. we now show that infection of mϕs from myd88(-/-) mice with sb(r)ld gave rise to sign ...201526283478
immunological comparison of dna vaccination using two delivery systems against canine leishmaniasis.visceral leishmaniasis (vl) is a fatal disease caused by the intracellular protozoan parasite leishmania infantum. dogs are the primary reservoirs of this parasite, and vaccination of dogs could be an effective method to reduce its transfer to humans. in order to develop a vaccine against vl (apart from the choice of immunogenic candidate antigens), it is necessary to use an appropriate delivery system to promote a proper antigen-specific immune response. in this study, we compared two vaccine d ...201526255093
a proteomic map of the unsequenced kala-azar vector phlebotomus papatasi using cell line.the debilitating disease kala-azar or visceral leishmaniasis is caused by the kinetoplastid protozoan parasite leishmania donovani. the parasite is transmitted by the hematophagous sand fly vector of the genus phlebotomus in the old world and lutzomyia in the new world. the predominant phlebotomine species associated with the transmission of kala-azar are phlebotomus papatasi and phlebotomus argentipes. understanding the molecular interaction of the sand fly and leishmania, during the developmen ...201526307495
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