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 assaysRuxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens
Carnes H, Mehrkens B, Stegman M, Rajagopalan G. Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens. The Journal Of Immunology 2019, 202: 190.34-190.34. DOI: 10.4049/jimmunol.202.supp.190.34.Peer-Reviewed Original ResearchSystemic inflammatory response syndromeMulti-organ failureT cellsHLA-DR3 transgenic miceHLA class II moleculesVehicle-treated miceVivo studiesInflammatory response syndromeT cell subsetsToxic shock syndromeJAK 1/2 inhibitorSelective JAK1/2 inhibitorClass II moleculesStaphylococcus aureusDose-dependent mannerSerious diseaseJanus kinaseIL-17Response syndromeOrgan failureJAK1/2 inhibitorActivation markersCell subsetsShock syndromeIL-2
2018
Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice
Rajagopalan G, Krogman A, Chowdhary V. Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice. The Journal Of Immunology 2018, 200: 117.3-117.3. DOI: 10.4049/jimmunol.200.supp.117.3.Peer-Reviewed Original ResearchHLA-DR3 transgenic miceToxic shock syndromeIL-17Transgenic miceHLA-DR3Shock syndromeAdaptive T cell responsesStaphylococcal toxic shock syndromeIL-17 family membersT cell responsesRole of IFNStaphylococcus aureus infectionS. aureusNon-specific activationTh17 cellsSerum levelsHLA-DRMice succumbedSystemic elevationTh1 cellsAureus infectionTissue injuryT cellsInfectious agentsIFN
2017
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
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
HLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia.
Rajagopalan G, Karau M, Krogman A, Patel R, David C. HLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia. The Journal Of Immunology 2016, 196: 66.9-66.9. DOI: 10.4049/jimmunol.196.supp.66.9.Peer-Reviewed Original ResearchSAg staphylococcal enterotoxin BT cell activationStaphylococcus aureus pneumoniaT cellsCell activationAureus pneumoniaStaphylococcal pneumoniaSerum cytokine/chemokine levelsCytokine/chemokine levelsHLA-DR3 transgenic miceT-cell activation markersEarly T cell activation markerRole of superantigensCell activation markersT cell subsetsTiming of administrationS. aureus strainsStaphylococcal enterotoxin BChemokine levelsDifferent time pointsHLA-DR3Activation markersCell subsetsCD69 expressionExperimental pneumonia
2015
Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia
Chung J, Greenwood-Quaintance K, Karau MJ, Tilahun A, Khaleghi SR, Chowdhary VR, David CS, Patel R, Rajagopalan G. Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia. Journal Of Leukocyte Biology 2015, 98: 271-281. PMID: 25979434, PMCID: PMC4501677, DOI: 10.1189/jlb.4a1214-577rr.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatheter-Related InfectionsCatheters, IndwellingCD4-Positive T-LymphocytesEnterotoxinsGene DeletionHistocompatibility AntigensHumansKidneyLiverLungLymphocyte ActivationMiceMice, TransgenicReceptors, Antigen, T-Cell, alpha-betaSpleenStaphylococcal InfectionsStaphylococcus aureusSuperantigensConceptsS. aureusHLA-DR3 transgenic miceLong intravenous catheterSystemic immune activationSerum cytokine levelsSystemic inflammatory diseaseAbsence of bacteremiaMHC class II moleculesInvasive staphylococcal diseaseToxigenic S. aureusClinical S. aureus isolatesS. aureus isolatesClass II moleculesIsogenic S. aureusCytokine levelsHLA-DR3Immune activationInflammatory diseasesIntravenous cathetersStaphylococcal diseaseRole of SAgsDevice-associated infectionsT cellsClinical consequencesForeign body
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 responseChronic activation with a staphylococcal superantigen drives the expansion of CD4, CD8 double negative T cells and promotes multiorgan inflammation mimicking systemic lupus erythematosus in HLA class II transgenic mice. (HUM7P.306)
Rajagopalan G, Tilahun A, Chowdhary V. Chronic activation with a staphylococcal superantigen drives the expansion of CD4, CD8 double negative T cells and promotes multiorgan inflammation mimicking systemic lupus erythematosus in HLA class II transgenic mice. (HUM7P.306). The Journal Of Immunology 2014, 192: 184.15-184.15. DOI: 10.4049/jimmunol.192.supp.184.15.Peer-Reviewed Original ResearchSystemic lupus erythematosusDNT cellsT cellsDKO miceLupus erythematosusKnockout miceCD8 coreceptorCD8 double-negative T cellsHLA class II transgenic miceTransgenic miceDouble-negative T cellsHLA-DR3 transgenic miceII transgenic miceRole of superantigensExpansion of CD4Role of CD4Negative T cellsLupus-like diseaseMini-osmotic pumpsPathogenesis of lupusWild-type miceSingle knockout miceDouble knockout miceT cell activationStaphylococcal enterotoxin B
2012
Detrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13)
Rajagopalan G, Tilahun A. Detrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13). The Journal Of Immunology 2012, 188: 164.13-164.13. DOI: 10.4049/jimmunol.188.supp.164.13.Peer-Reviewed Original ResearchToxic shock syndromeHLA-DR3 transgenic miceTreg numbersShock syndromeNon-menstrual toxic shock syndromeTransgenic miceCytokine/chemokine stormStaphylococcal toxic shock syndromeNumber of TregsMultiple organ failureStaphylococcal enterotoxin BChemokine stormMIP-1βOrgan failureMIP-1αUntreated groupSuperantigen exotoxinsDay 5Immune systemDay 0IL2CMiceEnterotoxin BStreptococcus pyogenesAdministration
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
Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies
Tilahun M, Rajagopalan G, Shah-Mahoney N, Lawlor R, Tilahun A, Xie C, Natarajan K, Margulies D, Ratner D, Osborne B, Goldsby R. Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies. Infection And Immunity 2010, 78: 2801-2811. PMID: 20308304, PMCID: PMC2876561, DOI: 10.1128/iai.01121-09.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BT cell receptorT cell populationsT cell activationHLA-DR3 transgenic miceMouse mAbsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsEnterotoxin BCross-linking T-cell receptorsAntigen-independent proliferationClass II major histocompatibility complex moleculesBlood mononuclear cellsAntigen-presenting cellsChimeric human-mouse antibodyMajor histocompatibility complex moleculesT cell proliferationAntigen-independent activationHistocompatibility complex moleculesAnti-SEB antibodiesCytokine productionMononuclear cellsCytokine secretionMHC-IIPotent neutralization
2008
Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice
Rajagopalan G, Epstein B, Lytle A, David C. Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice. The FASEB Journal 2008, 22: 848.11-848.11. DOI: 10.1096/fasebj.22.1_supplement.848.11.Peer-Reviewed Original ResearchToxic shock syndromeRegulatory T cellsHLA-DR3 transgenic miceT cellsTransgenic miceHLA class II transgenic miceDepletion of TregsII transgenic miceSerum cytokine levelsStaphylococcal enterotoxin BTreg cellsCytokine levelsIL-17Regulatory cellsSEB challengeIL-21IL-22Systemic exposureIL-6Shock syndromeIL-2IL-2RSplenic expressionTGF-b1Toxic shock
2006
Intranasal 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