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 differencesThe 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
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 responseThe Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection
Wetzel DM, McMahon-Pratt D, Koleske AJ. The Abl and Arg Kinases Mediate Distinct Modes of Phagocytosis and Are Required for Maximal Leishmania Infection. Molecular And Cellular Biology 2012, 32: 3176-3186. PMID: 22665498, PMCID: PMC3434515, DOI: 10.1128/mcb.00086-12.Peer-Reviewed Original ResearchConceptsComplement receptor 3Leishmania infectionIgG-coated beadsMurine cutaneous leishmaniasisPotential therapeutic targetLeishmania uptakeVisceral diseaseObligate intracellular parasitesCutaneous leishmaniasisTherapeutic targetFc receptorsAmastigote uptakeTreatment resultsReceptor 3Small lesionsInfection severityLeishmania amazonensisKinase inhibitorsIntracellular parasitesBead phagocytosisPhagocytosisReceptorsC3biInfectionLeishmaniasis
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 cells
1991
Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama.
Kreutzer R, Corredor A, Grimaldi G, Grogl M, Rowton E, Young D, Morales A, McMahon-Pratt D, Guzman H, Tesh R. Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama. American Journal Of Tropical Medicine And Hygiene 1991, 44: 662-75. PMID: 1677544, DOI: 10.4269/ajtmh.1991.44.662.Peer-Reviewed Original ResearchConceptsNew parasiteRestriction endonuclease fragment patternsPhlebotomine sand fliesKinetoplast DNASand fliesFragment patternsMolecular criteriaNew memberL. braziliensis complexL. lainsoniSpFliesBraziliensis complexPanamaParasitesIsoenzyme electrophoresisGenusMonoclonal antibodiesDNAMembersSlothsCharacterizationElectrophoresisLainsoniIsolates
1989
I. Extracellular Cultivation and Morphological Characterization of Amastigote‐Like Forms of Leishmania panamensis and L. braziliensis
EPERON S, McMAHON‐PRATT D. I. Extracellular Cultivation and Morphological Characterization of Amastigote‐Like Forms of Leishmania panamensis and L. braziliensis. Journal Of Eukaryotic Microbiology 1989, 36: 502-510. PMID: 2810145, DOI: 10.1111/j.1550-7408.1989.tb01086.x.Peer-Reviewed Original Research