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 studiesThe Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection
Wetzel DM, Rhodes EL, Li S, McMahon-Pratt D, Koleske AJ. The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. Journal Of Cell Science 2016, 129: 3130-3143. PMID: 27358479, PMCID: PMC5004897, DOI: 10.1242/jcs.185595.Peer-Reviewed Original ResearchMeSH KeywordsAniline CompoundsAnimalsCytokinesDisease Models, AnimalImatinib MesylateImmunoglobulin GLeishmaniaLeishmaniasisMacrophagesMiceModels, BiologicalNitrilesParasitesPhagocytosisPhosphorylationProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-hckPyrimidinesQuinolinesRAW 264.7 CellsSignal TransductionSrc-Family KinasesConceptsAmastigote uptakeObligate intracellular parasite LeishmaniaImmunoglobulin-mediated phagocytosisIntracellular parasite LeishmaniaNovel therapeutic strategiesPersistence of infectionLeishmania infectionIgG-mediated phagocytosisTherapeutic strategiesFc receptorsSmall molecule inhibitorsArg activationDisease severityParasite burdenPrimary macrophagesMacrophagesKinase inhibitorsLeishmaniasisHuman hostDevastating diseaseInfectionParasite LeishmaniaSrc family kinasesPhagocytosisLeishmania
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 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
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
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 electrophoresisInfectionLeishmaniasisCellular trafficking in trypanosomatids: a new target for therapies?
Costa-Pinto D, Trindade L, McMahon-Pratt D, Traub-Cseko Y. Cellular trafficking in trypanosomatids: a new target for therapies? International Journal For Parasitology 2001, 31: 537-544. PMID: 11334939, DOI: 10.1016/s0020-7519(01)00145-x.Peer-Reviewed Original ResearchConceptsPathogenic trypanosomatidsTrafficking mechanismsLysosomal targetingCellular trafficking mechanismsPlethora of diseasesCellular traffickingTrypanosomatidsTargeting mechanismCysteine proteinasesBiological aspectsNew targetsCurrent knowledgeEfficient vaccineDisease controlTherapyBasic mechanismsTraffickingMechanismTargetParasitesVaccineProteinasesDiseaseTargeting
2000
Evidence for a recent mutation giving rise to a truncated copy of a cysteine proteinase gene in Leishmania pifanoi
Boukai L, McMahon-Pratt D, Traub-Cseko Y. Evidence for a recent mutation giving rise to a truncated copy of a cysteine proteinase gene in Leishmania pifanoi. Parasitology International 2000, 49: 301-307. PMID: 11077264, DOI: 10.1016/s1383-5769(00)00060-x.Peer-Reviewed Original ResearchThe Immunologically Protective P-4 Antigen ofLeishmania Amastigotes A DEVELOPMENTALLY REGULATED SINGLE STRAND-SPECIFIC NUCLEASE ASSOCIATED WITH THE ENDOPLASMIC RETICULUM*
Kar S, Soong L, Colmenares M, Goldsmith-Pestana K, McMahon-Pratt D. The Immunologically Protective P-4 Antigen ofLeishmania Amastigotes A DEVELOPMENTALLY REGULATED SINGLE STRAND-SPECIFIC NUCLEASE ASSOCIATED WITH THE ENDOPLASMIC RETICULUM*. Journal Of Biological Chemistry 2000, 275: 37789-37797. PMID: 10969068, DOI: 10.1074/jbc.m002149200.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumSpecific nuclease activityBlot analysisImmunofluorescence microscopic analysisIntracellular amastigote stageProtein sequence dataSingle-strand nucleasePeripheral blood mononuclear cellsSouthern blot analysisNorthern blot analysisBlood mononuclear cellsMembrane proteinsRNA stabilitySubcellular localizationFuture vaccine studiesDNA repairSequence dataTerminal domainAmerican cutaneous leishmaniasisSequence analysisNuclease activityAmastigote stagePromastigote stageSpecific nucleasesT helperMolecular 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 ResearchTrafficking of cysteine proteinase to Leishmania lysosomes: lack of involvement of glycosylation
Boukai L, da Costa-Pinto D, Soares M, McMahon-Pratt D, Traub-Cseko Y. Trafficking of cysteine proteinase to Leishmania lysosomes: lack of involvement of glycosylation. Molecular And Biochemical Parasitology 2000, 107: 321-325. PMID: 10779610, DOI: 10.1016/s0166-6851(99)00233-9.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 cellsMonoclonal antibodies for the identification of New World Leishmania species
Grimaldi G, McMahon-Pratt D. Monoclonal antibodies for the identification of New World Leishmania species. Memórias Do Instituto Oswaldo Cruz 1996, 91: 37-42. PMID: 8734946, DOI: 10.1590/s0074-02761996000100006.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements