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 production
2013
The role of regulatory T cells in the Leishmania (Viannia) panamensis mouse model: a target for immunotherapy. (P3091)
Ehrlich A, Castilho T, Goldsmith-Pestana K, Sparwasser T, McMahon-Pratt D. The role of regulatory T cells in the Leishmania (Viannia) panamensis mouse model: a target for immunotherapy. (P3091). The Journal Of Immunology 2013, 190: 187.17-187.17. DOI: 10.4049/jimmunol.190.supp.187.17.Peer-Reviewed Original ResearchIL-17IL-10Treg functionIL-13Mouse modelMixed Th1/Th2Ablation of TregsL. panamensis infectionsRegulatory T cellsTh1/Th2Treg suppressive functionAlternate treatment strategiesT cell proliferationAmelioration of diseaseDEREG micePanamensis infectionTreg impairmentTreg cellsAdoptive transferCpG treatmentDisease resolutionHyperinflammatory responseNaïve miceDisease progressionTreatment strategies
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