2020
Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection
Bae J, Da F, Liu R, He L, Lv H, Fisher E, Rajagopalan G, Li M, Cheung G, Otto M. Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection. The Journal Of Infectious Diseases 2020, 223: 1766-1775. PMID: 32937658, PMCID: PMC8161638, DOI: 10.1093/infdis/jiaa584.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BS. aureus pathogenesisCommunity-associated methicillin-resistant S. aureus infectionsMethicillin-resistant S. aureus infectionsEnterotoxin BS. aureus infectionMouse infection modelDrug development strategiesCytokine stormFatal exacerbationStaphylococcus aureus systemic infectionSuperantigenic toxinsAureus infectionMajor human pathogenST59 isolatesSystemic infectionInfection modelVirulence potentialInfectionStaphylococcus aureusPathogenesisHuman pathogensSEBExacerbationIsolates
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
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
2014
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)
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
2013
Chronic Sub-Cutaneous Exposure to a Staphylococcus Aureus Superantigen, Staphylococcal Enterotoxin B, Elicits an Eosinophilic Airway Inflammation in HLA Class II Transgenic Mice - Linking Atopic Dermatitis (AD) to Asthma
Rajagopalan G, Tilahun A, Iijima K, Kita H. Chronic Sub-Cutaneous Exposure to a Staphylococcus Aureus Superantigen, Staphylococcal Enterotoxin B, Elicits an Eosinophilic Airway Inflammation in HLA Class II Transgenic Mice - Linking Atopic Dermatitis (AD) to Asthma. Journal Of Allergy And Clinical Immunology 2013, 131: ab331. DOI: 10.1016/j.jaci.2012.12.1559.Peer-Reviewed Original Research
2012
Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus
Chowdhary VR, Tilahun AY, Clark CR, Grande JP, Rajagopalan G. Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus. The Journal Of Immunology 2012, 189: 2054-2062. PMID: 22798666, PMCID: PMC3462343, DOI: 10.4049/jimmunol.1201097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensAutoimmune DiseasesCD28 AntigensCD4-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFlow CytometryFluorescent Antibody TechniqueHLA-DQ AntigensHumansInfusions, SubcutaneousLupus Erythematosus, SystemicMiceMice, TransgenicStaphylococcus aureusSuperantigensConceptsSystemic lupus erythematosusT cellsChronic exposureStaphylococcal enterotoxin BLupus erythematosusMouse MHC class II moleculesHLA-DQ8 transgenic miceMultisystem autoimmune inflammatory diseaseEnterotoxin BHLA-DQ8 miceAutoimmune inflammatory diseaseMHC class II moleculesTh1-type cytokinesMini-osmotic pumpsMononuclear cell infiltrationAnti-nuclear AbsClass II moleculesAbsence of diseaseChronic nasalIL-12Inflammatory infiltrateAutoimmune diseasesCell infiltrationInflammatory diseasesPathogenic roleDetrimental 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 B
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-kappaBPotent 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
2009
Therapeutic use of proteasome inhibitors in bacterial superantigen- and LPS-induced acute systemic inflammatory response syndromes (93.13)
rajagopalan G, Tilahun A, David C. Therapeutic use of proteasome inhibitors in bacterial superantigen- and LPS-induced acute systemic inflammatory response syndromes (93.13). The Journal Of Immunology 2009, 182: 93.13-93.13. DOI: 10.4049/jimmunol.182.supp.93.13.Peer-Reviewed Original ResearchToxic shock syndromeAcute systemic inflammatory response syndromeHLA class II transgenic miceProfound systemic inflammatory responseSystemic inflammatory response syndromeTherapeutic useAcute systemic inflammatory diseaseII transgenic miceInflammatory response syndromeSystemic inflammatory diseaseSystemic inflammatory responseAcute liver failureProteasome inhibitorsPro-inflammatory cytokinesT cell activationSerum biochemical parametersStaphylococcal enterotoxin BPro-apoptotic effectsLiver failureResponse syndromeSerum levelsHistopathological findingsCytokine productionSepsis modelShock syndromeEarly gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor
Rajagopalan G, Tilahun A, Asmann Y, David C. Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor. Physiological Genomics 2009, 37: 279-293. PMID: 19336531, PMCID: PMC2685500, DOI: 10.1152/physiolgenomics.90385.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBoronic AcidsBortezomibCytokinesEnterotoxinsGene Expression ProfilingGene Expression RegulationHLA-DR alpha-ChainsHLA-DR AntigensInflammation MediatorsMiceMice, TransgenicOligonucleotide Array Sequence AnalysisProtease InhibitorsPyrazinesReceptors, ChemokineReceptors, CytokineSignal TransductionSuperantigensConceptsToxic shock syndromePathogenesis of TSSStaphylococcal enterotoxin BBacterial superantigen staphylococcal enterotoxin BSuperantigen staphylococcal enterotoxin BEnterotoxin BAdministration of bortezomibAnti-inflammatory mediatorsTh17-type cytokinesProteasome inhibitorsCytokines/chemokinesSerious systemic illnessTransgenic mouse modelSuitable animal modelEarly gene expression changesNF-kappaB pathwaySystemic illnessSerum levelsShock syndromeImmunoregulatory cytokinesBacterial superantigensCC chemokinesMouse modelVivo administrationAnimal models
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
2007
Derivation of synergistically acting, neutralizing, chimeric human-mouse anti-SEB monoclonal antibodies (47.35)
Tilahun M, Rajagopalan G, Osborne B, Goldsby R. Derivation of synergistically acting, neutralizing, chimeric human-mouse anti-SEB monoclonal antibodies (47.35). The Journal Of Immunology 2007, 178: s73-s73. DOI: 10.4049/jimmunol.178.supp.47.35.Peer-Reviewed Original ResearchStaphylococcal enterotoxin BEffects of SEBMonoclonal antibodiesChimeric human-mouse antibodyT cell proliferationSecretion of cytokinesT cell activationMouse monoclonal antibodySEB intoxicationHuman IVIgSynergistic neutralizationCell activationChimeric antibodyLower potencyAnti-SEB monoclonal antibodiesEnterotoxin BAntibodiesCell proliferationFood poisoningPotential agentSP2/0 cellsS. aureusNIH grantsCell linesHuman IgH
2006
Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock
Rajagopalan G, Smart M, Murali N, Patel R, David C. Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock. Journal Of Reproductive Immunology 2006, 73: 51-59. PMID: 17070600, DOI: 10.1016/j.jri.2006.06.007.Peer-Reviewed Original ResearchConceptsMenstrual toxic shock syndromeSystemic immune activationHLA class II transgenic miceStaphylococcal enterotoxin BII transgenic miceImmune activationToxic shock syndromeSuperantigenic exotoxinsShock syndromeVaginal administrationTransgenic miceAcute systemic inflammatory diseaseSystemic inflammatory diseaseToxic shock syndrome toxinPeripheral lymphoid organsSEB-reactiveVaginal exposureProinflammatory cytokinesConjunctival routeLeukocytic infiltrationProfound elevationInflammatory diseasesLymphoid organsStaphylococcal superantigensT cellsAcute Systemic Immune Activation following Conjunctival Exposure to Staphylococcal Enterotoxin B
Rajagopalan G, Smart M, Patel R, David C. Acute Systemic Immune Activation following Conjunctival Exposure to Staphylococcal Enterotoxin B. Infection And Immunity 2006, 74: 6016-6019. PMID: 16988282, PMCID: PMC1594882, DOI: 10.1128/iai.00671-06.Peer-Reviewed Original ResearchINTRANASAL 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
2005
Endogenous Superantigens Shape Response to Exogenous Superantigens
Rajagopalan G, Singh M, Sen M, Murali N, Nath K, David C. Endogenous Superantigens Shape Response to Exogenous Superantigens. MSphere 2005, 12: 1119-1122. PMID: 16148182, PMCID: PMC1235787, DOI: 10.1128/cdli.12.9.1119-1122.2005.Peer-Reviewed Original Research