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
A monomeric fab fragment capable of inducing CD3 conformational change increases T cell receptor reactivity to poorly immunogenic antigens (TUM2P.1020)
Hoffmann M, Parks C, Hansen M, Rajagopalan G, Pease L, Schrum A, Gil Pages D. A monomeric fab fragment capable of inducing CD3 conformational change increases T cell receptor reactivity to poorly immunogenic antigens (TUM2P.1020). The Journal Of Immunology 2015, 194: 69.17-69.17. DOI: 10.4049/jimmunol.194.supp.69.17.Peer-Reviewed Original ResearchTCR/CD3Conformational changesCD3 complexT cell responsesProductive T cell responsesT cellsMature T cellsImmunogenic antigensCell responsesTCR engagementT cell activationTCR/MHC interactionsElicit signalingAnti-melanoma responsePMHC ligandsTg T cellsContext of vaccinationMonovalent Fab fragmentsMonomeric Fab fragmentsFab fragmentsSignal 2Cell activationPeptide ligandsCellsMetastatic melanoma
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
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
Interferon 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
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 syndrome
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
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
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