2016
Leishmania‐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 differences
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 productionCD4 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
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 organisms
2008
Intradermal 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
1998
Leishmania Amastigote Target Antigens: The Challenge of a Stealthy Intracellular Parasite
McMahon-Pratt D, Kima P, Soong L. Leishmania Amastigote Target Antigens: The Challenge of a Stealthy Intracellular Parasite. Trends In Parasitology 1998, 14: 31-34. PMID: 17040687, DOI: 10.1016/s0169-4758(97)01164-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsClass II presentation pathwayAmastigote stageMHC class ILeishmanial vaccineLeishmanial antigensAntigen presentationT cellsElicit protectionImmunized hostsPresentation pathwayInfected macrophagesMolecular vaccinesVaccine targetsInfected mammalian hostsClass IIntracellular parasitesVaccineInfectionCandidate moleculesMacrophagesMammalian hostsDevelopmental formsImmunizationAntigenLeishmaniasis
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 cellsDisruption of CD40–CD40 Ligand Interactions Results in an Enhanced Susceptibility to Leishmania amazonensis Infection
Soong L, Xu J, Grewal I, Kima P, Sun J, Longley B, Ruddle N, McMahon-Pratt D, Flavell R. Disruption of CD40–CD40 Ligand Interactions Results in an Enhanced Susceptibility to Leishmania amazonensis Infection. Immunity 1996, 4: 263-273. PMID: 8624816, DOI: 10.1016/s1074-7613(00)80434-3.Peer-Reviewed Original ResearchConceptsCD40L-/- miceImmune responseCD40-CD40 ligand interactionCD40L knockout miceLeishmania amazonensis infectionProgressive ulcerative lesionTissue parasite burdenCD40-CD40L interactionCellular immune responsesProtective immune responseWild-type miceHost immune responseImpaired T cellNitric oxide productionAmazonensis infectionUlcerative lesionsInflammatory responseNecrosis factorCD40 ligandT cellsIFN-gammaKnockout miceMacrophage activationParasite burdenOxide productionLeishmania 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