2023
Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2
Ihedioha O, Sivakoses A, Beverley S, McMahon-Pratt D, Bothwell A. Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2. Frontiers In Immunology 2023, 14: 1257046. PMID: 37885890, PMCID: PMC10598878, DOI: 10.3389/fimmu.2023.1257046.Peer-Reviewed Original ResearchConceptsLeukocyte-platelet aggregatesEarly immune responseImmune responsePlatelet activationHost's early immune responseCell-mediated immune responsesTh2 cell polarizationAdaptive immune responsesPro-inflammatory responsePattern recognition receptorsKey virulence factorsRecognition receptorsInfectious diseasesPathogenic moleculesEndothelial cellsWnt antagonistsInfection siteVirulence factorsTLR1/2PlateletsDickkopf1Cell typesLipophosphoglycanActivationResponse
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 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
CD4 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
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
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
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
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 epitopes
1996
Disruption 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 production
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
1988
Membrane glycoprotein M-2 protects against Leishmania amazonensis infection
Champsi J, McMahon-Pratt D. Membrane glycoprotein M-2 protects against Leishmania amazonensis infection. Infection And Immunity 1988, 56: 3272-3279. PMID: 3182080, PMCID: PMC259734, DOI: 10.1128/iai.56.12.3272-3279.1988.Peer-Reviewed Original ResearchConceptsMouse strainsComplete protectionBALB/c strainLeishmania amazonensis infectionT cell immunityProtective immune responseOnset of infectionC. parvumAmazonensis infectionInfecting doseProtective immunityChallenge infectionC57BL/6 miceAntibody responseCBA miceComplete adjuvantEffective adjuvantImmune responseImmunized animalsLog phase promastigotesLevel of protectionL. amazonensisInfectionC strainLeishmania amazonensis