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 ResearchMeSH KeywordsAnimalsEnterotoxinsMethicillin-Resistant Staphylococcus aureusMiceStaphylococcal InfectionsVirulenceConceptsStaphylococcal 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
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 response
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 BHuman 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 strainsInterferon 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
2009
Early 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
CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK
Rajagopalan G, Asmann Y, Lytle A, Tilahun A, Theuer J, Smart M, Patel R, David C. CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK. Shock 2008, 30: 721-728. PMID: 18496243, DOI: 10.1097/shk.0b013e31817048f7.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTherapeutic inhibitionAcute systemic inflammatory responseSevere toxic shock syndromeCytokine/chemokine productionT-cell activation/proliferationPotent T cell activatorsStrong immune activationMultiple organ dysfunctionSystemic inflammatory responseCOX-2 pathwayTransgenic mouse modelActivation/proliferationT cell activatorsT cell activationAgent of bioterrorismOrgan dysfunctionChemokine productionImmune activationFamily of exotoxinsShock syndromeEffective therapyInflammatory responseMicroarray-based gene expression profilingCOX-2
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
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
Expression 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
Expression and Function of Transgenic HLA-DQ Molecules and Lymphocyte Development in Mice Lacking Invariant Chain
Rajagopalan G, Smart M, Krco C, David C. Expression and Function of Transgenic HLA-DQ Molecules and Lymphocyte Development in Mice Lacking Invariant Chain. The Journal Of Immunology 2002, 169: 1774-1783. PMID: 12165499, DOI: 10.4049/jimmunol.169.4.1774.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigensAntigens, Differentiation, B-LymphocyteB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCytoskeletal ProteinsEnterotoxinsGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHumansIn Vitro TechniquesInterferon-gammaLymphocyte ActivationLymphocyte SubsetsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicShock, SepticConceptsClass II moleculesStaphylococcal enterotoxin BMHC class II moleculesT cellsFunctional MHC class II moleculesSystemic IFN-gamma productionT cell responsesHuman class II moleculesIFN-gamma productionPrimed T cellsHLA-DQ moleculesInvariant chainSpecific T cell hybridomasProcessing/presentationT cell hybridomasT cell developmentDQ8 miceExogenous superantigensHLA-DQ8Mature B cellsCytokine productionHLA-DQ6Phenotype of miceVivo challengeB cells