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 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 MAPKInfiltrationInfectionThe 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
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
T-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 cells