2019
Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality
Park K, Greenwood-Quaintance K, Cunningham S, Rajagopalan G, Chia N, Jeraldo P, Mandrekar J, Patel R. Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality. Microbial Pathogenesis 2019, 133: 103543. PMID: 31102653, DOI: 10.1016/j.micpath.2019.103543.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsBacteremiaBacterial AdhesionBase SequenceCell ProliferationDrug Resistance, BacterialFemaleHLA-DR3 AntigenHumansImmune EvasionMaleMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicMiddle AgedMinnesotaPolymerase Chain ReactionStaphylococcal InfectionsStaphylococcus aureusSuperantigensVirulenceVirulence FactorsConceptsMethicillin-susceptible S. aureusS. aureus bacteremiaAureus bacteremiaMedical CenterHLA-DR3 transgenic miceStaphylococcus aureus bacteremiaMinnesota Medical CenterLarge medical centerImmune evasion genesVirulence genesVirulence gene profilesNumber of deathsClinical dataClinical valueTransgenic miceClinical practiceIndividual PCR assaysWhole-genome sequencing analysisMortalitySAg genesSurvivorsLack of correlationBacteremiaWGS analysisFunctional assays
2017
Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen
Chowdhary VR, Krogman A, Tilahun AY, Alexander MP, David CS, Rajagopalan G. Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen. The Journal Of Immunology 2017, 198: 4413-4424. PMID: 28468970, PMCID: PMC5471834, DOI: 10.4049/jimmunol.1601991.Peer-Reviewed Original ResearchConceptsDNT cellsDKO miceClass II moleculesΑβ TCRT cellsBacterial superantigensCD8 coreceptorIntact MHC class ILupus-like autoimmune diseaseEnterotoxin BHLA-DQ8 moleculesMHC class II moleculesAnti-nuclear AbsPeripheral T cellsDouble knockout miceMurine MHC class II moleculesMHC class IThymic positive selectionStaphylococcal enterotoxin BCD4/CD8 coreceptorsRegulatory cellsHLA-DR3Splenic CD3WT miceAutoimmune diseasesPassive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus
Karau M, Tilahun M, Krogman A, Osborne B, Goldsby R, David C, Mandrekar J, Patel R, Rajagopalan G. Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus. Virulence 2017, 8: 1148-1159. PMID: 27925510, PMCID: PMC5711449, DOI: 10.1080/21505594.2016.1267894.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceSystemic inflammatory responseOnset of infectionLethal pneumoniaTransgenic miceInflammatory responseB antibodiesHLA class II transgenic miceStrong systemic immune responsePolyclonal human IgGII transgenic miceRobust T cell activationSystemic immune responsesPro-inflammatory cytokinesLethal toxic shockAnti-toxin antibodiesToxigenic Staphylococcus aureusHuman IgGS. aureusStaphylococcus aureusT cell activationAnti-SEB antibodiesStaphylococcal enterotoxin BConventional mouse strainsProphylactic administration
2016
Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model
Sheen Y, Rajagopalan G, Snapper C, Kita H, Wi C, Umaretiya P, Juhn Y. Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. HLA 2016, 88: 25-34. PMID: 27506953, PMCID: PMC6326101, DOI: 10.1111/tan.12851.Peer-Reviewed Original ResearchConceptsHouse dust miteHumoral immune responseAnti-pneumococcal polysaccharideHLA-DR polymorphismImmune responseHDM sensitizationIntact pneumococciHLA-DR3IgG responsesSerum titersTransgenic miceIntranasal house dust miteAnti-phosphorylcholine IgMHLA-DR3 miceLower humoral immune responseHalf of miceTransgenic mouse modelAllergic sensitizationPneumococcal diseaseIgM responseDR3 miceDust mitePneumococcal polysaccharideMouse modelA-IgG
2015
A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus
Chowdhary VR, Dai C, Tilahun AY, Hanson JA, Smart MK, Grande JP, Rajagopalan G, Fu SM, David CS. A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus. The Journal Of Immunology 2015, 195: 4660-4667. PMID: 26475924, PMCID: PMC5292932, DOI: 10.4049/jimmunol.1501073.Peer-Reviewed Original ResearchConceptsHLA-DR3NZM2328 miceClass IIMouse modelEndogenous MHC class IIAnti-dsDNA titersWire-loop lesionsSystemic lupus erythematosusSpecific HLA allelesMHC class IITransgenic mouse modelAnti-Sm AbsLupus erythematosusSevere proteinuriaAutoimmune responseHLA-DR2Lymphoid aggregatesAntibody responseHLA-DR3 moleculesHistological scoresT cellsImmune responseSpontaneous lupusHLA allelesHuman studies
2014
Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome
Tilahun AY, Chowdhary VR, David CS, Rajagopalan G. Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome. The Journal Of Immunology 2014, 193: 2919-2930. PMID: 25092888, PMCID: PMC4157092, DOI: 10.4049/jimmunol.1400980.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodiesAntigen-Antibody ComplexEnterotoxinsGlucocorticoid-Induced TNFR-Related ProteinGlucocorticoidsHLA-DR alpha-ChainsHLA-DR beta-ChainsHLA-DR3 AntigenInterferon-gammaInterleukin-17Interleukin-2Lymphocyte ActivationMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicReceptors, Tumor Necrosis FactorShock, SepticStaphylococcal InfectionsSuperantigensT-Lymphocytes, RegulatoryUp-RegulationConceptsToxic shock syndromeEndogenous TregsRegulatory cellsShock syndromeT cellsGlucocorticoid-induced TNFR family-related receptorCommunity-acquired methicillin-resistant strainsEx vivoHLA-DR3 transgenic miceSerum IFN-γ levelsFailure of TregsSystemic inflammatory responseIL-2/T regulatory (Treg) cellsIFN-γ levelsConventional T cellsLife-threatening infectionsMethicillin-resistant strainsT cell activationS. aureus strainsTreg numbersAdoptive transferIL-17Immune activationInflammatory responseThe Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia
Tilahun A, Karau M, Ballard A, Gunaratna M, Thapa A, David C, Patel R, Rajagopalan G. The Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia. Mediators Of Inflammation 2014, 2014: 468285. PMID: 25024509, PMCID: PMC4082930, DOI: 10.1155/2014/468285.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsHLA-DQ8 transgenic miceHeat-killed Staphylococcus aureusToxic shock syndromeStaphylococcal superantigensHLA-DR3Shock syndromeMolecular patternsTransgenic miceS. aureus-derived peptidoglycanSerious S. aureus infectionsCytokine/chemokine responsesLipoteichoic acidStaphylococcal toxic shock syndromeS. aureusLife-threatening systemic diseaseAnti-inflammatory roleT cell expansionS. aureus infectionT cell proliferationToxigenic S. aureusStaphylococcus aureusAdaptive immune systemChemokine responsesSystemic disease
2012
The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
Tilahun A, Karau M, Clark C, Patel R, Rajagopalan G. The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. Microbes And Infection 2012, 14: 528-536. PMID: 22273732, DOI: 10.1016/j.micinf.2012.01.001.Peer-Reviewed Original ResearchConceptsStaphylococcal superantigensT cell activationChemokine levelsCell activationSystemic inflammatory response syndromeDR3 transgenic miceEfficacy of tacrolimusInflammatory response syndromeHuman leukocyte antigenImpact of tacrolimusPotent immunosuppressive agentPost-exposure treatmentT cell proliferationS. aureus strainsSystemic cytokinesGut dysfunctionSerum cytokinesResponse syndromeImmunosuppressive agentsLeukocyte antigenSystemic pathologyTacrolimusLethal pneumoniaPneumoniaTransgenic mice
2011
Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB
Tilahun M, Kwan A, Natarajan K, Quinn M, Tilahun A, Xie C, Margulies D, Osborne B, Goldsby R, Rajagopalan G. Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB. PLOS ONE 2011, 6: e27203. PMID: 22102880, PMCID: PMC3216929, DOI: 10.1371/journal.pone.0027203.Peer-Reviewed Original ResearchConceptsToxic shock syndromeLethal toxic shock syndromeHLA-DR3 transgenic miceStaphylococcal enterotoxin BChimeric human-mouse antibodyShock syndromeT cellsVivo protectionTransgenic micePartial protectionComplete protectionLethal dosesT cell populationsClass II MHCSignificant partial protectionAnti-SEB antibodiesHuman T cellsOnly partial protectionInflammatory cytokinesClinical safetyII MHCB antibodiesVivo modelChimeric antibodyEnterotoxin BHLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD
Deshmukh U, Sim D, Dai C, Kannapell C, Gaskin F, Rajagopalan G, David C, Fu S. HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. Journal Of Autoimmunity 2011, 37: 254-262. PMID: 21868195, PMCID: PMC3372418, DOI: 10.1016/j.jaut.2011.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAutoantibodiesAutoantigensAutoimmunityEpitopes, T-LymphocyteFemaleHLA-DR3 AntigenHumansHybridomasImmunizationLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, TransgenicMolecular MimicryPeptidesProtein BindingSnRNP Core ProteinsStreptococcus agalactiaeT-LymphocytesVibrio choleraeConceptsSystemic lupus erythematosusHLA-DR3 transgenic miceT cell epitopesHLA-DR3T cellsEpitope levelCell epitopesTransgenic miceMolecular mimicryPathogenesis of SLET cell epitope mimicryAutoreactive T cell clonesT hybridomasHLA-DR3 miceMicrobial peptidesAutoreactive T cellsProduction of autoantibodiesT cell responsesT cell clonesLupus erythematosusLupus autoantigensAutoimmune responseAutoimmune disordersImmunized miceEpitope mimicryHuman Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome
Tilahun A, Marietta E, Wu T, Patel R, David C, Rajagopalan G. Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome. American Journal Of Pathology 2011, 178: 2760-2773. PMID: 21641398, PMCID: PMC3124354, DOI: 10.1016/j.ajpath.2011.02.033.Peer-Reviewed Original ResearchConceptsToxic shock syndromeShock syndromeTransgenic miceSmall intestineHLA-DR3 transgenic miceHLA class II moleculesMultiple organ inflammationPotent T cell activatorsKey pathogenic eventClass II moleculesT cell activatorsGut dysfunctionKawasaki diseaseLiver failureHeavy infiltrationHigh morbidityD-GalN.Pathologic changesT lymphocytesExtrahepatic pathologyPathogenic eventsAbsorptive functionD-galactosamineSensitization modelMouse strainsHLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation
Rajagopalan G, Tilahun A, Iijima K, David C, Kita H, Juhn Y. HLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation. HLA 2011, 77: 589-592. PMID: 21447115, DOI: 10.1111/j.1399-0039.2010.01617.x.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceHouse dust miteDust miteTransgenic miceTh2-predominant immune responseHouse dust mite extractInterleukin-13 levelsInflammatory cell countsBronchoalveolar lavage fluidTh2-type inflammationTransgenic mouse modelHLA-DR polymorphismAirway inflammationCytokine levelsBAL fluidEosinophil countHLA-DR3Childhood asthmaHLA-DR2Lavage fluidMite extractHLA-DRB1Immune responseInterleukin-4Mouse modelInterferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome
Tilahun A, Holz M, Wu T, David C, Rajagopalan G. Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome. PLOS ONE 2011, 6: e16764. PMID: 21304813, PMCID: PMC3033413, DOI: 10.1371/journal.pone.0016764.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTransgenic miceShock syndromePathogenesis of TSSSmall intestineLethal toxic shock syndromeHLA-DR3 transgenic miceSystematic histopathological examinationSystemic cytokine stormMultiple organ dysfunctionRobust T cell activationSevere inflammatory changesSmall bowel pathologyT cell expansionAnti-inflammatory propertiesSignificant pathological changesT cell activationIFN-γ geneGut permeabilityCytokine stormSEB challengeBowel pathologyInflammatory changesOrgan dysfunctionIntestinal pathology
2010
Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation
Tilahun A, Theuer J, Patel R, David C, Rajagopalan G. Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation. Molecular Therapy 2010, 18: 1143-1154. PMID: 20372109, PMCID: PMC2889741, DOI: 10.1038/mt.2010.53.Peer-Reviewed Original ResearchConceptsToxic shock syndromeStaphylococcal enterotoxin BNF-kappaB activationSystemic inflammationSerum levelsBacterial superantigensKappaB activationElevated TNF-alpha levelsTNF-alpha levelsAcute liver failureProteasome inhibitorsSevere systemic inflammationNuclear factor-kappaBSerum biochemical parametersTNF-alpha-induced cell deathSerum TNFLiver failureHistopathological findingsUntreated miceShock syndromeProphylactic useMurine modelImportant cytokineBortezomibFactor-kappaB
2006
INTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE
Rajagopalan G, Sen M, Singh M, Murali N, Nath K, Iijima K, Kita H, Leontovich A, Gopinathan U, Patel R, David C. INTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE. Shock 2006, 25: 647-656. PMID: 16721274, DOI: 10.1097/01.shk.0000209565.92445.7d.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesEnterotoxinsGene Expression RegulationHLA-DR3 AntigenHumansInflammationLungMiceMice, KnockoutNeutrophil InfiltrationReceptors, Interleukin-2Receptors, Interleukin-4Signal TransductionSystemic Inflammatory Response SyndromeConceptsII transgenic miceHLA class II transgenic miceStaphylococcal enterotoxin BCD8 T cellsTransgenic miceIntranasal exposureIL-12T cellsIFN-gammaEndogenous class II moleculesSystemic inflammatory response syndromeTCR V beta 8Defective IL-12Serum IFN-gammaSystemic immune activationInflammatory response syndromeSystemic cytokine responseBronchoalveolar lavage fluidMononuclear cell infiltrationPoor immune responsePro-inflammatory cytokinesS. aureus colonizationClass II moleculesIL-4 receptorNeutrophil influxIntranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice
Rajagopalan G, Iijima K, Singh M, Kita H, Patel R, David C. Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice. Infection And Immunity 2006, 74: 1284-1296. PMID: 16428778, PMCID: PMC1360368, DOI: 10.1128/iai.74.2.1284-1296.2006.Peer-Reviewed Original ResearchConceptsHLA-DQ8 transgenic miceStaphylococcal enterotoxin BSystemic immune activationAirway inflammationIntranasal exposureTransgenic miceImmune activationIntranasal routeSuperantigen exotoxinsHLA class II transgenic miceHLA-DR3 transgenic miceMajor histocompatibility complex class IIBALB/c miceHistocompatibility complex class IIHLA-DR3 miceII transgenic miceInduces airway inflammationEosinophilic airway inflammationNeutrophilic airway inflammationEosinophilic inflammatory responseStreptococcal pyrogenic exotoxinMurine major histocompatibility complex class IIAirway destructionSerious infectionsC mice
2004
In Vitro and In Vivo Evaluation of Staphylococcal Superantigen Peptide Antagonists
Rajagopalan G, Sen M, David C. In Vitro and In Vivo Evaluation of Staphylococcal Superantigen Peptide Antagonists. Infection And Immunity 2004, 72: 6733-6737. PMID: 15501813, PMCID: PMC522998, DOI: 10.1128/iai.72.11.6733-6737.2004.Peer-Reviewed Original Research
2003
Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans
Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans. International Immunology 2003, 15: 1035-1044. PMID: 12917255, DOI: 10.1093/intimm/dxg103.Peer-Reviewed Original ResearchConceptsCo-stimulatory molecules B7-1Incidence of diabetesTransgenic miceB7-1Autoimmune diabetesHLA-DQ8HLA-DR3T cellsBeta cellsBeta-cell toxin streptozotocinHLA class II associationsDQ8 transgenic micePresence of DR3HLA transgenic miceAntibody-mediated depletionPathogenesis of T1D.Class II associationsHLA class IIWhole-body irradiationPancreatic beta cellsNon-specific activationSpontaneous diabetesToxin streptozotocinDiabetogenic potentialSTZ treatmentExpression and function of HLA‐DR3 and DQ8 in transgenic mice lacking functional H2‐M
Rajagopalan G, Smart M, Cheng S, Krco C, Johnson K, David C. Expression and function of HLA‐DR3 and DQ8 in transgenic mice lacking functional H2‐M. HLA 2003, 62: 149-161. PMID: 12889995, DOI: 10.1034/j.1399-0039.2003.00088.x.Peer-Reviewed Original Research
2002
Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II
Kudva Y, Rajagopalan G, Raju R, Abraham R, Smart M, Hanson J, David C. Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. Human Immunology 2002, 63: 987-999. PMID: 12392851, DOI: 10.1016/s0198-8859(02)00435-4.Peer-Reviewed Original ResearchConceptsType 1 diabetesEndogenous class II moleculesClass II moleculesHLA-DR3NOD miceHuman leukocyte antigen (HLA) transgenic miceTransgenic miceEndogenous MHC class IICyclophosphamide-induced diabetesIntra-islet infiltrationMultiple low dosesDouble transgenic miceGroups of miceMHC class IINonobese diabetic (NOD) backgroundTransgenic expressionSpontaneous diabetesDiabetic backgroundUnmanipulated miceDQ8DiabetesLow dosesClass IILess infiltrationMice