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 ResearchMeSH KeywordsAnimalsCytokinesDelayed-Action PreparationsFemaleImmunologic FactorsLeishmaniaLeishmaniasisMiceMice, Inbred BALB CNanoparticlesTreatment OutcomeConceptsPathogen-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 studiesLeishmania‐encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence
Holowka T, Castilho TM, Garcia AB, Sun T, McMahon‐Pratt D, Bucala R. Leishmania‐encoded orthologs of macrophage migration inhibitory factor regulate host immunity to promote parasite persistence. The FASEB Journal 2016, 30: 2249-2265. PMID: 26956417, PMCID: PMC4871794, DOI: 10.1096/fj.201500189r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteApoptosisCD4-Positive T-LymphocytesCloning, MolecularGene DeletionGene Expression RegulationHistocompatibility Antigens Class IILeishmania majorLeishmaniasis, CutaneousMacrophage Migration-Inhibitory FactorsMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, SCIDOrganisms, Genetically ModifiedProtein Array AnalysisProtozoan ProteinsConceptsMacrophage migration inhibitory factorMigration inhibitory factorCD4 T cellsInhibitory factorL. majorT cellsHost immunityProtective CD4 T cellsEffector CD4 T cellsCytokine macrophage migration inhibitory factorMajor-infected miceT cell primingAntigen-presenting cellsT cell formationExpression of IFNDeath-1Functional exhaustionIL-7RHost responseParasite persistenceParasite burdenParasite growthReduced expressionMiceSignificant differencesThe 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
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 production
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
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 counterpartsIntradermal NKT cell activation during DNA priming in heterologous prime‐boost vaccination enhances T cell responses and protection against Leishmania
Dondji B, Deak E, Goldsmith‐Pestana K, Perez‐Jimenez E, Esteban M, Miyake S, Yamamura T, McMahon‐Pratt D. Intradermal NKT cell activation during DNA priming in heterologous prime‐boost vaccination enhances T cell responses and protection against Leishmania. European Journal Of Immunology 2008, 38: 706-719. PMID: 18286565, PMCID: PMC3448375, DOI: 10.1002/eji.200737660.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigens, ProtozoanCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesGalactosylceramidesGenetic VectorsGranzymesImmunity, CellularInterferon-gammaInterleukin-10Killer Cells, NaturalLeishmaniasisLymphocyte ActivationLymphocyte DepletionMiceMice, Inbred BALB CMice, Mutant StrainsNitric OxideProtozoan ProteinsSkinT-LymphocytesVaccinationVaccines, DNAVaccinia virusConceptsHeterologous prime-boost vaccinationPrime-boost vaccinationNKT cell activationCD8 T cellsT cellsCell activationVaccinated miceDNA primingActivated C-kinase (rLACK) antigensT cell immune responsesDevelopment of CD4Murine cutaneous leishmaniasisT cell responsesCell immune responsesElicit protective immunityIL-10Protective immunityImmune responseLeishmania homologueIFN-gammaAlphaGalCerCutaneous leishmaniasisVisceral leishmaniasisParasite burdenCell responses
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 ResearchMeSH KeywordsAnimalsAntigens, ProtozoanFemaleGlycolipidsLeishmaniaMembrane ProteinsMiceMice, Inbred BALB CProteolipidsProtozoan ProteinsProtozoan VaccinesConceptsAntigen 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
Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis
Kima P, Constant S, Hannum L, Colmenares M, Lee K, Haberman A, Shlomchik M, McMahon-Pratt D. Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis. Journal Of Experimental Medicine 2000, 191: 1063-1068. PMID: 10727468, PMCID: PMC2193117, DOI: 10.1084/jem.191.6.1063.Peer-Reviewed Original ResearchConceptsFc receptorsB cell antigen presentationMurine cutaneous leishmaniasisFunctional B cellsCommon gamma chainL. mexicana complexLeishmania infectionAntigen presentationCutaneous leishmaniasisB cellsLeishmania pathogenesisInfectionComplex parasitesCritical roleAntibodiesMexicana complexPathogenesisMiceGamma chainReceptorsParasitesLeishmaniasis
1996
Leishmania amazonensis:Cultivation and Characterization of Axenic Amastigote-like Organisms
Hodgkinson V, Soong L, Duboise S, McMahon-Pratt D. Leishmania amazonensis:Cultivation and Characterization of Axenic Amastigote-like Organisms. Experimental Parasitology 1996, 83: 94-105. PMID: 8654556, DOI: 10.1006/expr.1996.0053.Peer-Reviewed Original ResearchConceptsAmastigote-like formsNorthern blot analysisDevelopmental biologyContinual cultureAxenic cultureMolecular biologyTransformation of promastigotesOrganismsDNA probesGeneration timeCultured amastigotesAxenic cultivationBlot analysisExpression levelsSpecies of LeishmaniaSpeciesProtein reactiveBiologyDegrees CFirst reportPeriod of growthAmastigotesPromastigotesLeishmania amazonensisCultivation
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
1990
Prophylactic Immunization against Experimental Leishmania donovani Infection by Use of a Purified Protein Vaccine
White A, McMahon-Pratt D. Prophylactic Immunization against Experimental Leishmania donovani Infection by Use of a Purified Protein Vaccine. The Journal Of Infectious Diseases 1990, 161: 1313-1314. PMID: 2345310, DOI: 10.1093/infdis/161.6.1313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ProtozoanAntigens, ProtozoanFemaleLeishmania donovaniLeishmaniasis, VisceralMiceMice, Inbred BALB CProtozoan ProteinsVaccination
1989
Amastigote and epimastigote stage-specific components of Trypanosoma cruzi characterized by using monoclonal antibodies. Purification and molecular characterization of an 83-kilodalton amastigote protein.
Pan A, McMahon-Pratt D. Amastigote and epimastigote stage-specific components of Trypanosoma cruzi characterized by using monoclonal antibodies. Purification and molecular characterization of an 83-kilodalton amastigote protein. The Journal Of Immunology 1989, 143: 1001-8. PMID: 2501384, DOI: 10.4049/jimmunol.143.3.1001.Peer-Reviewed Original ResearchConceptsTissue culture-derived trypomastigotesTrypanosoma cruziCruzi amastigotesPreliminary sequence dataStage-specific componentsCulture-derived trypomastigotesStage-specific monoclonal antibodiesSingle protein moleculesMembrane-enriched preparationsAmino acid compositionSequence dataEpimastigote membranesHuman chagasic seraStage differentiationAxenic cultureMolecular characterizationT. cruzi amastigotesEpimastigotesProtein moleculesProteinChagas diseaseMonoclonal antibodiesLeishmania speciesAcid compositionChagasic seraMonoclonal Antibodies Specific for Members of the Genus Endotrypanum
LOPES A, McMAHON‐PRATT D. Monoclonal Antibodies Specific for Members of the Genus Endotrypanum. Journal Of Eukaryotic Microbiology 1989, 36: 354-361. PMID: 2504911, DOI: 10.1111/j.1550-7408.1989.tb05526.x.Peer-Reviewed Original Research
1988
Monoclonal antibodies specific for the amastigote stage of Leishmania pifanoi. I. Characterization of antigens associated with stage- and species-specific determinants.
Pan A, McMahon-Pratt D. Monoclonal antibodies specific for the amastigote stage of Leishmania pifanoi. I. Characterization of antigens associated with stage- and species-specific determinants. The Journal Of Immunology 1988, 140: 2406-14. PMID: 2450920, DOI: 10.4049/jimmunol.140.7.2406.Peer-Reviewed Original Research
1984
Production and characterization of species-specific monoclonal antibodies against Leishmania donovani for immunodiagnosis.
Jaffe C, Bennett E, Grimaldi G, McMahon-Pratt D. Production and characterization of species-specific monoclonal antibodies against Leishmania donovani for immunodiagnosis. The Journal Of Immunology 1984, 133: 440-7. PMID: 6373932, DOI: 10.4049/jimmunol.133.1.440.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesVisceral leishmaniasisSpecies-specific monoclonal antibodiesL. donovaniAntibody DAntigenic determinantsLeishmania donovaniKala-azar serumWestern blot analysisSpecies of LeishmaniaSerologic assaysEpidemiologic studiesClinical diagnosisWestern blotAntigenic moleculesProtein antigensRadioimmunoprecipitation analysisAntibodiesLeishmaniasisLeishmania speciesLeishmania stocksDonovaniMonoclonal antibody DBlot analysisAntigen
1983
Monoclonal antibodies specific for Leishmania tropica. I. Characterization of antigens associated with stage- and species-specific determinants.
Jaffe C, McMahon-Pratt D. Monoclonal antibodies specific for Leishmania tropica. I. Characterization of antigens associated with stage- and species-specific determinants. The Journal Of Immunology 1983, 131: 1987-93. PMID: 6194223, DOI: 10.4049/jimmunol.131.4.1987.Peer-Reviewed Original ResearchConceptsSpecies-specific determinantsPromastigote stageDifferent cell surface proteinsCell surface proteinsMonoclonal antibody bindsMembrane-enriched preparationsCell surface componentsL. tropica complexAdditional proteinsKilodalton proteinClone TTrypanosoma cruziSurface proteinsProteinMonoclonal antibodiesIntact promastigotesSurface componentsSolubilized 125IL. donovaniL. braziliensis braziliensisMajor promastigotesL. mexicana amazonensisPromastigotesI. CharacterizationCruziIn vivo protection against Leishmania mexicana mediated by monoclonal antibodies.
Anderson S, David J, McMahon-Pratt D. In vivo protection against Leishmania mexicana mediated by monoclonal antibodies. The Journal Of Immunology 1983, 131: 1616-8. PMID: 6619540, DOI: 10.4049/jimmunol.131.4.1616.Peer-Reviewed Original Research