2024
Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis
Fernández O, Rosales-Chilama M, Sánchez-Hidalgo A, Gómez P, Rebellón-Sánchez D, Regli I, Díaz-Varela M, Tacchini-Cottier F, Saravia N. Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis. PLOS Neglected Tropical Diseases 2024, 18: e0012156. PMID: 38709850, PMCID: PMC11098511, DOI: 10.1371/journal.pntd.0012156.Peer-Reviewed Original ResearchConceptsAssociated with treatment failureTreatment failureHost risk factorsBALB/c miceRisk factorsDrug susceptibilityClinical strainsOutcome of cutaneous leishmaniasisOdds of treatment failureMeglumine antimoniateParasitological response to treatmentLeishmania (Viannia) panamensisSubgroup of patientsAntimicrobial drug susceptibilityResponse to treatmentU937 macrophagesEvaluate drug susceptibilityCutaneous leishmaniasis patientsCutaneous leishmaniasisFailed treatmentPlasma CmaxTherapeutic responseClinical outcomesPatient's lesionsTreatment outcomes
2017
Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility
Barrera MC, Rojas LJ, Weiss A, Fernandez O, McMahon-Pratt D, Saravia NG, Gomez MA. Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility. Acta Tropica 2017, 176: 355-363. PMID: 28843396, PMCID: PMC5633519, DOI: 10.1016/j.actatropica.2017.08.017.Peer-Reviewed Original ResearchConceptsLeishmania resistanceDrug susceptibilityDrug resistanceHost cell gene expressionClinical strainsCell gene expressionExpression of ABCA2THP-1 cellsPrimary human macrophagesLeishmania susceptibilityGene expressionAntimonial drugsCutaneous leishmaniasisInfected macrophagesLeishmania panamensisIntracellular amastigotesHuman macrophagesResistant strainsSusceptible parasitesAntimonialsIntracellular parasitesLeishmania speciesMacrophagesL. panamensisAQP-9
2015
Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators
Gonzalez-Fajardo L, Fernández OL, McMahon-Pratt D, Saravia NG. Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators. PLOS Neglected Tropical Diseases 2015, 9: e0003820. PMID: 26024228, PMCID: PMC4449175, DOI: 10.1371/journal.pntd.0003820.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsOutcome of infectionIL-10Meglumine antimoniateIL-13Therapeutic strategiesAntileishmanial drugsTherapeutic responseCytokine secretionInfected peripheral blood mononuclear cellsParasite survivalHuman peripheral blood mononuclear cellsL. panamensis infectionsCutaneous leishmaniasis patientsPro-inflammatory cytokinesBlood mononuclear cellsIL-13 secretionIntracellular parasite survivalAssessment of hostViability of LeishmaniaEfficacy of treatmentPromising therapeutic strategySecretion of TNFInnovative therapeutic strategiesMonocyte-derived macrophages
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
2013
Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival
Gómez MA, Navas A, Márquez R, Rojas LJ, Vargas DA, Blanco VM, Koren R, Zilberstein D, Saravia NG. Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival. Journal Of Antimicrobial Chemotherapy 2013, 69: 139-149. PMID: 23975742, PMCID: PMC3861331, DOI: 10.1093/jac/dkt334.Peer-Reviewed Original ResearchConceptsIntracellular parasite survivalParasite survivalIntracellular pathogensRNA gene knockdownDrug response genesGene expression profilingHost cell mechanismsHost cell determinantsSurvival of LeishmaniaFunctional validationExpression profilingGene knockdownGene expressionDrug transportersQuantitative RT-PCRPhagolysosomal membraneOutcome of treatmentCell-mediated regulationIntracellular parasite killingNovel mechanismPharmacokinetics/pharmacodynamicsPrimary macrophagesMetallothionein 2AHuman macrophagesTransporters
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 responseNovel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp
Fernández O, Diaz-Toro Y, Valderrama L, Ovalle C, Valderrama M, Castillo H, Perez M, Saravia NG. Novel Approach to In Vitro Drug Susceptibility Assessment of Clinical Strains of Leishmania spp. Journal Of Clinical Microbiology 2012, 50: 2207-2211. PMID: 22518860, PMCID: PMC3405580, DOI: 10.1128/jcm.00216-12.Peer-Reviewed Original ResearchConceptsClinical strainsMeglumine antimoniateDrug susceptibilityCell ratioParasite burdenAntileishmanial drugsDrug susceptibility assessmentReduction of infectionParasites/cellIntracellular burdenAntimonial drugsLeishmania panamensisDrug concentrationsEffective dosesHuman macrophagesPresence of drugsL. braziliensisParasite growthHost cell ratioMiltefosineLeishmania sppDrugsL. guyanensisLeishmaniaAntimoniate
2011
Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis
Gallego C, Golenbock D, Gomez MA, Saravia NG. Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis. Infection And Immunity 2011, 79: 2871-2879. PMID: 21518783, PMCID: PMC3191987, DOI: 10.1128/iai.01388-10.Peer-Reviewed Original ResearchConceptsToll-like receptorsEndosomal Toll-like receptorsTNF-α productionMacrophage activationLeishmania panamensisTumor necrosis factor-alpha secretionNecrosis factor-alpha secretionHost macrophagesL. panamensis infectionsLack of TLR2Specific TLR ligandsBone marrow-derived macrophagesIntracellular parasite survivalTNF-α secretionMurine bone marrow-derived macrophagesMarrow-derived macrophagesHuman primary macrophagesEarly time pointsMyD88/Panamensis infectionMouse macrophage cell lineTLR4 expressionTLR ligandsHost cell responsesAlpha secretion
2000
Distinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection
Bosque, Saravia, Valderrama, Milon. Distinct Innate and Acquired Immune Responses to Leishmania in Putative Susceptible and Resistant Human Populations Endemically Exposed to L. (Viannia) panamensis Infection. Scandinavian Journal Of Immunology 2000, 51: 533-541. PMID: 10792848, DOI: 10.1046/j.1365-3083.2000.00724.x.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedDisease SusceptibilityEndemic DiseasesFemaleHumansHypersensitivity, DelayedImmunity, InnateInterferon-gammaInterleukin-10Leishmania guyanensisLeishmaniasis, MucocutaneousMacrophagesMaleMiddle AgedMonocytesRecombinant ProteinsRecurrenceRisk FactorsTritiumTumor Necrosis Factor-alphaConceptsPeripheral blood mononuclear cellsRecurrent diseaseL. panamensis infectionsCD8 T lymphocytesType hypersensitivity responseBlood mononuclear cellsAcquired Immune ResponsesTumor necrosis factorProduction of interferonEntry of parasitesLeishmania Viannia panamensisPanamensis infectionRecurrent leishmaniasisHypersensitivity responseImmunological basisSkin testMononuclear cellsNecrosis factorT lymphocytesImmune responseSubclinical infectionLinear regression analysisEvidence of differencesDistinct innateIntracellular amastigotes
1998
Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis.
Bosque F, Milon G, Valderrama L, Saravia N. Permissiveness of human monocytes and monocyte-derived macrophages to infection by promastigotes of Leishmania (Viannia) panamensis. Journal Of Parasitology 1998, 84: 1250-6. PMID: 9920322, DOI: 10.2307/3284682.Peer-Reviewed Original ResearchConceptsPercentage of cellsBlood monocytesInduction of differentiationLeishmania panamensis infectionHuman peripheral blood monocytesHistiocytic cell line UDifferentiated macrophagesExpression of CD68Number of amastigotesPeripheral blood monocytesOutcome of infectionSite of infectionMonocyte-derived macrophagesL. panamensis promastigotesMononuclear phagocytic cellsPhorbol myristate acetatePanamensis infectionNumber of parasitesCell line UBone marrowFresh monocytesLeishmania panamensisMonocytesResident macrophagesStages of differentiation
1990
Infectivity of the subspecies of the Leishmania braziliensis complex in vivo and in vitro.
Rey J, Travi B, Valencia A, Saravia N. Infectivity of the subspecies of the Leishmania braziliensis complex in vivo and in vitro. American Journal Of Tropical Medicine And Hygiene 1990, 43: 623-31. PMID: 2267967, DOI: 10.4269/ajtmh.1990.43.623.Peer-Reviewed Original Research