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
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 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
2008
A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses
Kamir D, Zierow S, Leng L, Cho Y, Diaz Y, Griffith J, McDonald C, Merk M, Mitchell RA, Trent J, Chen Y, Kwong YK, Xiong H, Vermeire J, Cappello M, McMahon-Pratt D, Walker J, Bernhagen J, Lolis E, Bucala R. A Leishmania Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses. The Journal Of Immunology 2008, 180: 8250-8261. PMID: 18523291, PMCID: PMC2668862, DOI: 10.4049/jimmunol.180.12.8250.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, Differentiation, B-LymphocyteApoptosis Regulatory ProteinsCell LineCells, CulturedCrystallography, X-RayHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesLeishmania majorMacrophage Migration-Inhibitory FactorsMacrophages, PeritonealMiceMice, Inbred BALB CMice, Inbred C3HMice, KnockoutMolecular Sequence DataRecombinant ProteinsStructural Homology, ProteinConceptsMacrophage migration inhibitory factorCD74-dependent mannerMigration inhibitory factorImmune defense mechanismsHuman macrophage migration inhibitory factorSmall molecule antagonistsActivation-induced apoptosisHost macrophage responseMIF receptorMIF proteinImmune destructionObligate intracellular parasitesMAP kinase activationERK1/2 MAP kinase activationInhibitory factorMacrophage responseLeishmania majorIntracellular parasitesHigh-resolution X-ray crystal structuresSpecies-specific inhibitionMacrophagesSignificant structural homologyKinase activationDefense mechanismsMammalian counterparts
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 species
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