2016
Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness
Abdeen S, Salim N, Mammadova N, Summers CM, Goldsmith-Pestana K, McMahon-Pratt D, Schultz PG, Horwich AL, Chapman E, Johnson SM. Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness. Bioorganic & Medicinal Chemistry Letters 2016, 26: 5247-5253. PMID: 27720295, DOI: 10.1016/j.bmcl.2016.09.051.Peer-Reviewed Original ResearchConceptsT. brucei infectionBrucei infectionComplex treatment regimensFirst-line drugsNew therapeutic strategiesLeishmania major promastigotesAnti-parasitic potentialTreatment regimensTherapeutic windowTherapeutic strategiesCurrent drugsMajor promastigotesEncouraging initial resultsHuman liverAntibiotic resistanceGreater cytotoxicityProtozoan parasiteKidney cellsMedicinal chemistry optimizationInfectionInhibitorsPotent inhibitorBrucei parasitesDrugsCytotoxicityThe 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
2012
The 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
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
2001
Biochemical and Biological Characterization of the Protective Leishmania pifanoi Amastigote Antigen P-8
Colmenares M, Tiemeyer M, Kima P, McMahon-Pratt D. Biochemical and Biological Characterization of the Protective Leishmania pifanoi Amastigote Antigen P-8. Infection And Immunity 2001, 69: 6776-6784. PMID: 11598050, PMCID: PMC100055, DOI: 10.1128/iai.69.11.6776-6784.2001.Peer-Reviewed Original ResearchConceptsAntigen PFurther vaccine studiesSignificant T cell activationT cell activationWestern blot analysisProtective immunityVaccine studiesApolipoprotein EMurine modelCutaneous leishmaniasisSignificant protectionComparable protectionImmunodominant componentAntigenic glycolipidsImmunity studiesAntigenCysteine proteinasesGlycolipid componentBiochemical analysisBiological characterizationSodium dodecyl sulfate-polyacrylamide gel electrophoresisDodecyl sulfate-polyacrylamide gel electrophoresisSulfate-polyacrylamide gel electrophoresisInfectionLeishmaniasis
2000
Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis
Kima P, Constant S, Hannum L, Colmenares M, Lee K, Haberman A, Shlomchik M, McMahon-Pratt D. Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis. Journal Of Experimental Medicine 2000, 191: 1063-1068. PMID: 10727468, PMCID: PMC2193117, DOI: 10.1084/jem.191.6.1063.Peer-Reviewed Original ResearchConceptsFc receptorsB cell antigen presentationMurine cutaneous leishmaniasisFunctional B cellsCommon gamma chainL. mexicana complexLeishmania infectionAntigen presentationCutaneous leishmaniasisB cellsLeishmania pathogenesisInfectionComplex parasitesCritical roleAntibodiesMexicana complexPathogenesisMiceGamma chainReceptorsParasitesLeishmaniasis
1998
Leishmania Amastigote Target Antigens: The Challenge of a Stealthy Intracellular Parasite
McMahon-Pratt D, Kima P, Soong L. Leishmania Amastigote Target Antigens: The Challenge of a Stealthy Intracellular Parasite. Trends In Parasitology 1998, 14: 31-34. PMID: 17040687, DOI: 10.1016/s0169-4758(97)01164-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsClass II presentation pathwayAmastigote stageMHC class ILeishmanial vaccineLeishmanial antigensAntigen presentationT cellsElicit protectionImmunized hostsPresentation pathwayInfected macrophagesMolecular vaccinesVaccine targetsInfected mammalian hostsClass IIntracellular parasitesVaccineInfectionCandidate moleculesMacrophagesMammalian hostsDevelopmental formsImmunizationAntigenLeishmaniasis
1990
Prophylactic Immunization against Experimental Leishmania donovani Infection by Use of a Purified Protein Vaccine
White A, McMahon-Pratt D. Prophylactic Immunization against Experimental Leishmania donovani Infection by Use of a Purified Protein Vaccine. The Journal Of Infectious Diseases 1990, 161: 1313-1314. PMID: 2345310, DOI: 10.1093/infdis/161.6.1313.Peer-Reviewed Original Research
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
1987
Leishmaniasis in Brazil: XXIII. The identification of Leishmania braziliensis braziliensis in wild-caught neotropical sandflies using monoclonal antibodies
Shaw J, Lainson R, Ryan L, Braga R, McMahon-Pratt D, David J. Leishmaniasis in Brazil: XXIII. The identification of Leishmania braziliensis braziliensis in wild-caught neotropical sandflies using monoclonal antibodies. Transactions Of The Royal Society Of Tropical Medicine And Hygiene 1987, 81: 69-72. PMID: 3445325, DOI: 10.1016/0035-9203(87)90287-2.Peer-Reviewed Original Research