2017
Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection
Ehrlich AK, Fernández OL, Rodriguez-Pinto D, Castilho TM, Caridad M, Goldsmith-Pestana K, Saravia NG, McMahon-Pratt D. Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection. Infection And Immunity 2017, 85: 10.1128/iai.00981-16. PMID: 28052994, PMCID: PMC5328479, DOI: 10.1128/iai.00981-16.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsPeripheral blood mononuclear cellsCutaneous leishmaniasisB cellsIL-17IL-13Inflammatory responseMouse modelToll-like receptor 9 ligand CpGAlternate therapeutic approachCurrent treatment optionsBlood mononuclear cellsMixed inflammatory responseRegulatory cell functionProduction of IFNPredominant etiologic agentDose-response effectHost immune responseCell populationsGrowth factor βCpG treatmentRegulatory cellsChemokine responsesIL-10Host Immune
2016
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness
Abdeen S, Salim N, Mammadova N, Summers CM, Goldsmith-Pestana K, McMahon-Pratt D, Schultz PG, Horwich AL, Chapman E, Johnson SM. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. Bioorganic & Medicinal Chemistry Letters 2016, 26: 5247-5253. PMID: 27720295, DOI: 10.1016/j.bmcl.2016.09.051.Peer-Reviewed Original ResearchConceptsT. brucei infectionBrucei infectionComplex treatment regimensFirst-line drugsNew therapeutic strategiesLeishmania major promastigotesAnti-parasitic potentialTreatment regimensTherapeutic windowTherapeutic strategiesCurrent drugsMajor promastigotesEncouraging initial resultsHuman liverAntibiotic resistanceGreater cytotoxicityProtozoan parasiteKidney cellsMedicinal chemistry optimizationInfectionInhibitorsPotent inhibitorBrucei parasitesDrugsCytotoxicityThe Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfection
2014
Chronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression
Navas A, Vargas DA, Freudzon M, McMahon-Pratt D, Saravia NG, Gómez MA. Chronicity of Dermal Leishmaniasis Caused by Leishmania panamensis Is Associated with Parasite-Mediated Induction of Chemokine Gene Expression. Infection And Immunity 2014, 82: 2872-2880. PMID: 24752514, PMCID: PMC4097649, DOI: 10.1128/iai.01133-13.Peer-Reviewed Original ResearchConceptsSelf-healed patientsChronic cutaneous leishmaniasisDermal leishmaniasisChemokine gene expressionClinical outcomesBiopsy specimensChronic diseasesInflammatory responseLeishmania panamensisExpression levelsCCR5 receptor geneInduction of CXCL5Montenegro skin testLesion biopsy specimensL. panamensisSelf-healing diseaseNew therapeutic targetsReverse transcription-quantitative PCRTranscription-quantitative PCRChemotactic chemokinesInflammation contributesSkin testAsymptomatic infectionInflammatory activationImmune cellsCD4 T cell activation by B cells in human Leishmania (Viannia)infection
Rodriguez-Pinto D, Saravia NG, McMahon-Pratt D. CD4 T cell activation by B cells in human Leishmania (Viannia)infection. BMC Infectious Diseases 2014, 14: 108. PMID: 24568275, PMCID: PMC3937821, DOI: 10.1186/1471-2334-14-108.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB-LymphocytesBiotinCD4-Positive T-LymphocytesColombiaFemaleFlow CytometryFluorescein-5-isothiocyanateGene Expression RegulationHumansImmunoglobulin MInterferon-gammaInterleukin-6Leishmania braziliensisLeishmaniasis, CutaneousLeukocytes, MononuclearLymphocyte ActivationMaleMiddle AgedOvalbuminTumor Necrosis Factor-alphaYoung AdultConceptsCD4 T cellsCutaneous leishmaniasis patientsT cellsB cellsLeishmaniasis patientsT cell activationLeishmania antigenImmune responseCell activationT-cell activation parametersSpecific CD4 T cellsEffective adaptive immune responseCD4 T cell activationB-cell activation markersCultures of PBMCUpregulation of CD86Cell activation markersCostimulatory molecule CD86Activation markers CD25Adaptive immune responsesHuman cutaneous leishmaniasisPurified B cellsT cell culturesHuman B cell linesHuman B cells
2012
Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response
Ramírez C, Díaz-Toro Y, Tellez J, Castilho TM, Rojas R, Ettinger NA, Tikhonova I, Alexander ND, Valderrama L, Hager J, Wilson ME, Lin A, Zhao H, Saravia NG, McMahon-Pratt D. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response. PLOS Neglected Tropical Diseases 2012, 6: e1866. PMID: 23145196, PMCID: PMC3493378, DOI: 10.1371/journal.pntd.0001866.Peer-Reviewed Original ResearchConceptsMRNA abundance profilesMonocyte-derived macrophagesRegulation of genesDistinct biologic responsesAbundance profilesL. panamensisDifferential gene expressionEarly time pointsMacrophage responseEarly macrophage responseImmune responseLeishmania speciesHuman monocyte-derived macrophagesMicroarray evidenceOutset of infectionGene regulationActivation of PKCHuman macrophage responseGene expressionLeishmania panamensis infectionTime pointsCellular responsesAdaptive immune responsesG proteinsEarly inflammatory response
2010
Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease
Castilho TM, Goldsmith‐Pestana K, Lozano C, Valderrama L, Saravia NG, McMahon‐Pratt D. Murine model of chronic L. (Viannia) panamensis infection: Role of IL‐13 in disease. European Journal Of Immunology 2010, 40: 2816-2829. PMID: 20827674, PMCID: PMC3289133, DOI: 10.1002/eji.201040384.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsChronic DiseaseDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFemaleHumansInterferon-gammaInterleukin-13LeishmaniaLeishmaniasis, CutaneousMaleMiceMice, Inbred BALB CMice, KnockoutMiddle AgedReceptors, Interleukin-4Th1 CellsTh2 CellsTumor Necrosis Factor-alphaYoung AdultConceptsL. panamensis infectionsIL-13Panamensis infectionChronic diseasesImmunodeficient miceMurine modelMixed Th1/Th2 responseBALB/c mouse modelTh1/Th2 responsePrevalent etiologic agentHuman cutaneous leishmaniasisPresence of TNFPrevention of leishmaniasisIL-17Immunological mechanismsTh2 responsesIL-10Recurrent lesionsChronic infectionEvident lesionsMice resemblesT cellsImmune responsePersistent infectionLeishmania organisms
2008
A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses
Kamir D, Zierow S, Leng L, Cho Y, Diaz Y, Griffith J, McDonald C, Merk M, Mitchell RA, Trent J, Chen Y, Kwong YK, Xiong H, Vermeire J, Cappello M, McMahon-Pratt D, Walker J, Bernhagen J, Lolis E, Bucala R. A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses. The Journal Of Immunology 2008, 180: 8250-8261. PMID: 18523291, PMCID: PMC2668862, DOI: 10.4049/jimmunol.180.12.8250.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, Differentiation, B-LymphocyteApoptosis Regulatory ProteinsCell LineCells, CulturedCrystallography, X-RayHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesLeishmania majorMacrophage Migration-Inhibitory FactorsMacrophages, PeritonealMiceMice, Inbred BALB CMice, Inbred C3HMice, KnockoutMolecular Sequence DataRecombinant ProteinsStructural Homology, ProteinConceptsMacrophage migration inhibitory factorCD74-dependent mannerMigration inhibitory factorImmune defense mechanismsHuman macrophage migration inhibitory factorSmall molecule antagonistsActivation-induced apoptosisHost macrophage responseMIF receptorMIF proteinImmune destructionObligate intracellular parasitesMAP kinase activationERK1/2 MAP kinase activationInhibitory factorMacrophage responseLeishmania majorIntracellular parasitesHigh-resolution X-ray crystal structuresSpecies-specific inhibitionMacrophagesSignificant structural homologyKinase activationDefense mechanismsMammalian counterparts
2004
Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease?
McMahon‐Pratt D, Alexander J. Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunological Reviews 2004, 201: 206-224. PMID: 15361243, DOI: 10.1111/j.0105-2896.2004.00190.x.Peer-Reviewed Original ResearchConceptsMajor histocompatibility complex classDistinct Leishmania speciesLeishmania major infectionResolution of infectionT cell responsesT helper 1Histocompatibility complex classDifferent virulence factorsHost defense mechanismsMajor infectionVisceral diseaseHost macrophage cellsImmune mechanismsVisceral organsParasitic protozoaVaccine developmentCutaneous leishmaniasesSusceptibility/resistanceIntracellular pathogensGenus LeishmaniaControl of diseaseInfectionMacrophage cellsDiseaseLeishmania speciesLeishmanial Amastigote Antigen P‐2 Induces Major Histocompatibility Complex Class II‐Dependent Natural Killer‐Cell Reactivity in Cells from Healthy Donors
Nylén S, Maasho K, McMahon‐Pratt D, Akuffo H. Leishmanial Amastigote Antigen P‐2 Induces Major Histocompatibility Complex Class II‐Dependent Natural Killer‐Cell Reactivity in Cells from Healthy Donors. Scandinavian Journal Of Immunology 2004, 59: 294-304. PMID: 15030581, DOI: 10.1111/j.0300-9475.2004.01388.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ProtozoanCD8-Positive T-LymphocytesFetal BloodHistocompatibility Antigens Class IIHumansInterferon-gammaInterleukin-10Killer Cells, NaturalLeishmaniaLeishmaniasisLymphocyte ActivationProtozoan VaccinesReceptors, IgGReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsHealthy donorsLeishmaniasis patientsAmerican cutaneous leishmaniasis patientsClass IIMajor histocompatibility complex class IIMajor histocompatibility complex classHistocompatibility complex class IIClass II antibodiesCutaneous leishmaniasis patientsInterleukin-10 productionNatural killer cellsProtective immune responseInterferon-gamma productionIFN-gamma responsesMHC class IIHistocompatibility complex classHealthy adult donorsDevelopment of vaccinesAdherent cell populationAmastigote antigensNatural killerKiller cellsCytokine productionCell reactivityLeishmania infection
2003
Evaluation of amastigote reactive cells in human cutaneous leishmaniasis caused by Leishmania aethiopica
MAASHO K, MCMAHON-PRATT D, RAITA J, RAUD M, BRITTON S, SOONG L, AKUFFO H. Evaluation of amastigote reactive cells in human cutaneous leishmaniasis caused by Leishmania aethiopica. Clinical & Experimental Immunology 2003, 132: 316-322. PMID: 12699423, PMCID: PMC1808716, DOI: 10.1046/j.1365-2249.2003.02165.x.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsCutaneous leishmaniasisNK cellsOld World cutaneous leishmaniasisEthiopian cutaneous leishmaniasisLeishmania parasite infectionIL-10 responsesPercentage of CD4IL-10 productionBlood mononuclear cellsHuman cutaneous leishmaniasisAmastigote antigensLymphoproliferative responsesLeishmaniasis patientsMain cell typesMononuclear cellsAntigen stimulationHuman leishmaniasisGamma interferonLeishmania aethiopicaReactive cellsProtective phenotypePatientsL. aethiopicaLeishmaniasis
2002
Heterogeneity, geographic distribution, and pathogenicity of serodemes of Leishmania viannia in Colombia.
Saravia NG, Weigle K, Navas C, Segura I, Valderrama L, Valencia AZ, Escorcia B, McMahon-Pratt D. Heterogeneity, geographic distribution, and pathogenicity of serodemes of Leishmania viannia in Colombia. American Journal Of Tropical Medicine And Hygiene 2002, 66: 738-44. PMID: 12224583, DOI: 10.4269/ajtmh.2002.66.738.Peer-Reviewed Original Research
2000
Molecular and biologic characterization of Leishmania parasites implicated in an epidemic outbreak in northwestern Argentina
Segura E, Juan N, Piquin A, Cuba Cuba C, Abramo Orrego L, McMahon-Pratt D, Montamat E, Momen H, Grimaldi Jr. G. Molecular and biologic characterization of Leishmania parasites implicated in an epidemic outbreak in northwestern Argentina. Parasitology Research 2000, 86: 504-508. PMID: 10894479, DOI: 10.1007/s004360050702.Peer-Reviewed Original Research
1998
Leishmania pifanoi Amastigote Antigen P-4: Epitopes Involved in T-Cell Responsiveness in Human Cutaneous Leishmaniasis
Haberer J, Da-Cruz A, Soong L, Oliveira-Neto M, Rivas L, McMahon-Pratt D, Coutinho S. Leishmania pifanoi Amastigote Antigen P-4: Epitopes Involved in T-Cell Responsiveness in Human Cutaneous Leishmaniasis. Infection And Immunity 1998, 66: 3100-3105. PMID: 9632572, PMCID: PMC108319, DOI: 10.1128/iai.66.7.3100-3105.1998.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsTh1-like responseCytokine productionCutaneous leishmaniasisExperimental murine cutaneous leishmaniasisTh1-like immune responseDetectable interleukin-4Leishmaniasis vaccine developmentCutaneous leishmaniasis patientsMurine cutaneous leishmaniasisBlood mononuclear cellsT cell responsivenessGamma interferon productionT cell proliferationIFN-gamma responsesHuman cutaneous leishmaniasisLeishmaniasis patientsMononuclear cellsImmune responseInterleukin-4Proliferative responseWhole parasite homogenatesIFN-gammaEpitope studiesMultiple epitopesT cell responses to crude and defined leishmanial antigens in patients from the Lower Amazon region of Brazil infected with different species of Leishmania of the subgenera Leishmania and Viannia
Silveira F, Blackwell J, Ishikawa E, Braga R, Shaw J, Quinnell R, Soong L, Kima P, McMahon‐Pratt D, Black G, Shaw M. T cell responses to crude and defined leishmanial antigens in patients from the Lower Amazon region of Brazil infected with different species of Leishmania of the subgenera Leishmania and Viannia. Parasite Immunology 1998, 20: 19-26. PMID: 9491414, DOI: 10.1046/j.1365-3024.1998.t01-1-00126.x.Peer-Reviewed Original ResearchConceptsT cell responsesDiffuse cutaneous leishmaniasisLeishmanial antigensCell responsesLCL patientsMucocutaneous leishmaniasisMCL patientsCutaneous leishmaniasisL. amazonensis antigensSkin test responsesL. braziliensis antigensSuitable vaccine candidateDCL patientsPoor respondersGood respondersPatient groupBraziliensis antigensSubgenus LeishmaniaAntigen A2Vaccine candidatesPatientsPotent stimulatorA2 antigenAntigenSignificant rise
1996
T-Cell Responsiveness of American Cutaneous Leishmaniasis Patients to PurifiedLeishmania pifanoiAmastigote Antigens andLeishmania braziliensisPromastigote Antigens: Immunologic Patterns Associated with Cure
Coutinho S, Oliveira M, Da-Cruz A, De Luca P, Mendonça S, Bertho A, Soong L, McMahon-Pratt D. T-Cell Responsiveness of American Cutaneous Leishmaniasis Patients to PurifiedLeishmania pifanoiAmastigote Antigens andLeishmania braziliensisPromastigote Antigens: Immunologic Patterns Associated with Cure. Experimental Parasitology 1996, 84: 144-155. PMID: 8932764, DOI: 10.1006/expr.1996.0100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ProtozoanAntimonyAntiprotozoal AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCytokinesFemaleHumansInterferon-gammaInterleukin-2Interleukin-4LeishmaniaLeishmania braziliensisLeishmaniasis, CutaneousLymphocyte ActivationMaleMeglumineMeglumine AntimoniateOrganometallic CompoundsT-LymphocytesConceptsT cell responsesEnd of therapyBeneficial T cell responsesCell responsesCytokine productionProliferative responseAmerican cutaneous leishmaniasis patientsType 1 cytokine productionType 2 cytokine productionPeripheral blood mononuclear cellsCutaneous leishmaniasis patientsType 1 cytokinesLymphocyte proliferative responsesBlood mononuclear cellsLow proliferative responseT cell responsivenessMixed type 1T cell stimulationAmerican cutaneous leishmaniasisImmunologic patternActive diseaseReactive CD4Amastigote antigensLeishmaniasis patientsMononuclear cells
1992
Cutaneous Leishmaniasis: Review of 59 Cases Seen at the National Institutes of Health
Melby P, Kreutzer R, McMahon-Pratt D, Gam A, Neva F. Cutaneous Leishmaniasis: Review of 59 Cases Seen at the National Institutes of Health. Clinical Infectious Diseases 1992, 15: 924-937. PMID: 1457663, DOI: 10.1093/clind/15.6.924.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisEndemic areasCutaneous diseaseGroup of patientsDiffuse cutaneous leishmaniasisNational InstituteDifferent endemic areasChronic relapsingFrequent international travelOptimal therapyClinical spectrumMultiple lesionsAmerican patientsLeishmaniasisPatientsLeishmania majorDiseaseLesionsEarly ageInternational travelU.S. residentsHealthRelapsingMajorityTherapyCutaneous leishmaniasis in western Venezuela caused by infection with Leishmania venezuelensis and L. braziliensis variants
Bonfante-Garrido R, Meléndez E, Barroeta S, de Alejos M, Momen H, Cupolillo E, McMahon-Pratt D, Grimaldi G. Cutaneous leishmaniasis in western Venezuela caused by infection with Leishmania venezuelensis and L. braziliensis variants. Transactions Of The Royal Society Of Tropical Medicine And Hygiene 1992, 86: 141-148. PMID: 1440772, DOI: 10.1016/0035-9203(92)90544-m.Peer-Reviewed Original ResearchConceptsL. braziliensisEndemic regionsSame endemic regionLeishmania venezuelensisL. venezuelensisSpecific monoclonal antibodiesCutaneous leishmaniasisPositive culturesEpidemiological studiesInfected donkeysHuman casesMonoclonal antibodiesDomestic reservoirBraziliensisL. guyanensisVenezuelensisState of LaraIsoenzyme electrophoresisReference strains
1991
Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama.
Kreutzer R, Corredor A, Grimaldi G, Grogl M, Rowton E, Young D, Morales A, McMahon-Pratt D, Guzman H, Tesh R. Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama. American Journal Of Tropical Medicine And Hygiene 1991, 44: 662-75. PMID: 1677544, DOI: 10.4269/ajtmh.1991.44.662.Peer-Reviewed Original ResearchConceptsNew parasiteRestriction endonuclease fragment patternsPhlebotomine sand fliesKinetoplast DNASand fliesFragment patternsMolecular criteriaNew memberL. braziliensis complexL. lainsoniSpFliesBraziliensis complexPanamaParasitesIsoenzyme electrophoresisGenusMonoclonal antibodiesDNAMembersSlothsCharacterizationElectrophoresisLainsoniIsolatesCharacterization and classification of leishmanial parasites from humans, wild mammals, and sand flies in the Amazon region of Brazil.
Grimaldi G, Momen H, Naiff R, McMahon-Pratt D, Barrett T. Characterization and classification of leishmanial parasites from humans, wild mammals, and sand flies in the Amazon region of Brazil. American Journal Of Tropical Medicine And Hygiene 1991, 44: 645-61. PMID: 1858968, DOI: 10.4269/ajtmh.1991.44.645.Peer-Reviewed Original Research