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
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
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
Comment on: Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation
Rajagopalan G, Patel R, Kaveri S, David C. Comment on: Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation. Journal Of Antimicrobial Chemotherapy 2006, 59: 157-159. PMID: 17071954, DOI: 10.1093/jac/dkl430.Peer-Reviewed Original ResearchAcute 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 cells
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 cellsStaphylococcal enterotoxin B‐induced activation and concomitant resistance to cell death in CD28‐deficient HLA‐DQ8 transgenic mice
Rajagopalan G, Smart M, Marietta E, David C. Staphylococcal enterotoxin B‐induced activation and concomitant resistance to cell death in CD28‐deficient HLA‐DQ8 transgenic mice. International Immunology 2002, 14: 801-812. PMID: 12096040, DOI: 10.1093/intimm/dxf047.Peer-Reviewed Original ResearchConceptsT cellsStaphylococcal enterotoxin BHLA-DQ8IFN-gammaTransgenic miceEnterotoxin BBALB/c splenocytesDQ8 transgenic miceSerum IFN-gammaLess IL-2IL-6 productionAbsence of CD28Role of CD28Activation-induced cell deathCertain effector functionsIL-10Lethal shockIL-2IL-4Immune responseEffector functionsConcomitant resistanceCD28Nitric oxideMice