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
Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model
Siefert AL, Ehrlich A, Corral MJ, Goldsmith-Pestana K, McMahon-Pratt D, Fahmy TM. Immunomodulatory nanoparticles ameliorate disease in the Leishmania (Viannia) panamensis mouse model. Biomaterials 2016, 108: 168-176. PMID: 27636154, PMCID: PMC5049880, DOI: 10.1016/j.biomaterials.2016.09.004.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsAccumulation of MDSCsHyper-inflammatory responseOngoing immune responseCytokine IL-10Antigen-presenting cellsCurrent treatment strategiesInflammation-mediated diseasesLong treatment regimensSite of infectionNew World leishmaniasisCellular immunomodulationIL-17Suppressor cellsDendritic cellsIL-10Immunotherapeutic approachesChronic inflammationTreatment regimensIL-13Free CpGTreatment strategiesTherapeutic effectImmune responsePreclinical studies
2014
The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection
Ehrlich A, Castilho TM, Goldsmith-Pestana K, Chae WJ, Bothwell AL, Sparwasser T, McMahon-Pratt D. The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection. The Journal Of Immunology 2014, 193: 2961-2970. PMID: 25098291, PMCID: PMC4170189, DOI: 10.4049/jimmunol.1400728.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesAntigen-Antibody ComplexCell ProliferationFemaleImmunotherapy, AdoptiveIndoleamine-Pyrrole 2,3,-DioxygenaseInflammationInterferon-gammaInterleukin-10Interleukin-13Interleukin-17Interleukin-2Leishmania guyanensisLeishmaniasis, MucocutaneousLymphocyte CountMiceMice, Inbred BALB CMice, TransgenicParasite LoadT-Lymphocytes, RegulatoryTransforming Growth Factor betaConceptsRegulatory T cellsPanamensis infectionInflammatory responseT cellsLeishmania parasitesDisease pathologyImmunotherapeutic treatment approachesL. panamensis infectionsLeishmania panamensis infectionPercentage of TregsRIL-2/Th2 inflammatory responseIL-13 levelsParasite loadAlternate treatment strategiesT cell proliferationTreg functionalityDisease exacerbationAdoptive transferIL-17IL-10Naive miceCytokine responsesImmunotherapeutic roleCytokine productionChronicity 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 KeywordsAdultAgedBiotinB-LymphocytesCD4-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
2011
TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia)
Jayakumar A, Castilho TM, Park E, Goldsmith-Pestana K, Blackwell JM, McMahon-Pratt D. TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia). PLOS Neglected Tropical Diseases 2011, 5: e1204. PMID: 21695103, PMCID: PMC3114751, DOI: 10.1371/journal.pntd.0001204.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDisease Models, AnimalFemaleGenetic VectorsImmunization, SecondaryInterferon-gammaInterleukin-10Interleukin-13LeishmaniaLeishmaniasisLeishmaniasis VaccinesMiceMice, Inbred BALB CPeroxidasesProtozoan ProteinsRodent DiseasesToll-Like Receptor 1Toll-Like Receptor 2VaccinationVaccines, DNAVaccines, SyntheticVaccinia virusViral VaccinesConceptsPrime-boost vaccinationHeterologous prime-boost vaccinationCD8 T cellsT cell responsesT cellsTLR1/2 activationIL-10Vaccination modalityIL-13Immune responseAntigen-specific CD8 cellsCD8 T cell responsesCell responsesL. panamensis infectionsSpecific CD8 cellsTLR1/2 agonist Pam3CSK4IL-10 responsesVaccine-induced protectionCD4 T cellsMurine immune responseIL-13 responsesLeishmania speciesInfection/diseaseVaccinia virus AnkaraInnate immune 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 organismsMurine visceral leishmaniasis: IgM and polyclonal B‐cell activation lead to disease exacerbation
Deak E, Jayakumar A, Cho KW, Goldsmith‐Pestana K, Dondji B, Lambris JD, McMahon‐Pratt D. Murine visceral leishmaniasis: IgM and polyclonal B‐cell activation lead to disease exacerbation. European Journal Of Immunology 2010, 40: 1355-1368. PMID: 20213734, PMCID: PMC2944234, DOI: 10.1002/eji.200939455.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ProtozoanAntigen PresentationB-LymphocytesComplement C5aDisease ProgressionFemaleHypergammaglobulinemiaImmunity, InnateImmunization, PassiveImmunoglobulin GImmunoglobulin MInterleukin-10Leishmania infantumLeishmaniasis, VisceralLymph NodesLymphocyte ActivationLymphocyte DepletionMaleMiceMice, Inbred BALB CMice, TransgenicParasitemiaConceptsBALB/c miceC miceDisease exacerbationImmune responseVisceral leishmaniasisB cell-derived IL-10WT BALB/c miceB cell antigen presentationPolyclonal B cell activationAnti-Leishmania responseOngoing immune responseL. infantum infectionHuman visceral leishmaniasisBALB/cB cell expansionIntradermal infection modelB cell activationEstablishment of infectionElevated parasitemiaParasite visceralizationCytokine levelsIL-10Infantum infectionPassive transferAntigen presentation
2006
Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis
Carrillo E, Ahmed S, Goldsmith-Pestana K, Nieto J, Osorio Y, Travi B, Moreno J, McMahon-Pratt D. Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis. Vaccine 2006, 25: 1534-1543. PMID: 17178178, PMCID: PMC2571115, DOI: 10.1016/j.vaccine.2006.10.036.Peer-Reviewed Original ResearchConceptsSoluble Leishmania antigenAmastigote antigensImmune responseAmerican cutaneous leishmaniasis patientsTh1-like immune responseSoluble leishmanial antigenCutaneous leishmaniasis patientsIL-4 mRNAAppropriate immune responseCanine visceral leishmaniasisElicit appropriate immune responsesIdentification of LeishmaniaGeneral vaccinesLeishmanial antigensIL-10Leishmania antigenLeishmaniasis patientsSLA antigensTNF-alphaDisease manifestationsIFN-gammaMurine modelMouse modelVisceral leishmaniasisLeishmania infantum
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
2001
Biochemical and Biological Characterization of the Protective Leishmania pifanoi Amastigote Antigen P-8
Colmenares M, Tiemeyer M, Kima P, McMahon-Pratt D. Biochemical and Biological Characterization of the Protective Leishmania pifanoi Amastigote Antigen P-8. Infection And Immunity 2001, 69: 6776-6784. PMID: 11598050, PMCID: PMC100055, DOI: 10.1128/iai.69.11.6776-6784.2001.Peer-Reviewed Original ResearchConceptsAntigen PFurther vaccine studiesSignificant T cell activationT cell activationWestern blot analysisProtective immunityVaccine studiesApolipoprotein EMurine modelCutaneous leishmaniasisSignificant protectionComparable protectionImmunodominant componentAntigenic glycolipidsImmunity studiesAntigenCysteine proteinasesGlycolipid componentBiochemical analysisBiological characterizationSodium dodecyl sulfate-polyacrylamide gel electrophoresisDodecyl sulfate-polyacrylamide gel electrophoresisSulfate-polyacrylamide gel electrophoresisInfectionLeishmaniasis
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
Leishmania‐infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells
Kima P, Soong L, Chicharro C, Ruddle N, McMahon‐Pratt D. Leishmania‐infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells. European Journal Of Immunology 1996, 26: 3163-3169. PMID: 8977318, DOI: 10.1002/eji.1830261249.Peer-Reviewed Original ResearchConceptsT cellsAntigen presentationParasite antigensMajor histocompatibility complex (MHC) class II moleculesMHC class II pathwayActivation of CD4Peritoneal exudate cellsClass II pathwayClass II moleculesHost immune systemCell linesT cell linesAmastigote antigensLeishmania antigenAntigen sequestrationLeishmania amastigotesMacrophage cell lineExudate cellsCD4Immune systemLive parasitesParasite moleculesAntigenMacrophagesInfected cellsT-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 cellsLeishmania amazonensis:The Asian Rhesus Macaques (Macaca mulatta) as an Experimental Model for Study of Cutaneous Leishmaniasis
Amaral V, Ransatto V, Conceição-Silva F, Molinaro E, Ferreira V, Coutinho S, McMahon-Pratt D, Grimaldi G. Leishmania amazonensis:The Asian Rhesus Macaques (Macaca mulatta) as an Experimental Model for Study of Cutaneous Leishmaniasis. Experimental Parasitology 1996, 82: 34-44. PMID: 8617329, DOI: 10.1006/expr.1996.0005.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisRhesus macaquesActive infectionPrimate modelT cellsPeripheral T-cell subpopulationsType hypersensitivity responseLevels of IgMT cell subpopulationsNonhuman primate modelCourse of infectionAsian rhesus macaquesLeishmanial antigensHomologous infectionMononuclear infiltrateProtective immunityHypersensitivity responseIgG antibodiesPathologic analysisLeishmanial infectionPlasma cellsSkin lesionsProliferative responseLesion sizeInitial infection
1995
Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis
Soong L, Duboise S, Kima P, McMahon-Pratt D. Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis. Infection And Immunity 1995, 63: 3559-3566. PMID: 7642292, PMCID: PMC173494, DOI: 10.1128/iai.63.9.3559-3566.1995.Peer-Reviewed Original ResearchConceptsBALB/c miceAmastigote antigensC miceImmune responseTh1 cell-mediated immune responseCell-mediated immune responsesCBA/J miceCross-species protectionGamma interferon productionWeeks of infectionAmastigotes of LeishmaniaHost immune responseStage-specific antigensAmazonensis infectionImmunized miceIntraperitoneal injectionJ miceCorynebacterium parvumLeishmaniasis vaccineProliferative responseVaccine potentialCutaneous leishmaniasisParasite burdenInterferon productionAntigen
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