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 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 ResearchMeSH KeywordsAnimalsHLA-DQ AntigensHLA-DR3 AntigenLymphocyte ActivationMice, TransgenicPneumoniaShock, SepticStaphylococcus aureusSuperantigensConceptsPathogen-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
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
HLA-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 mimicryInterferon 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
2007
Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice
Rajagopalan G, Polich G, Sen M, Singh M, Epstein B, Lytle A, Rouse M, Patel R, David C. Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice. HLA 2007, 71: 135-145. PMID: 18086265, DOI: 10.1111/j.1399-0039.2007.00986.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHLA-DQ AntigensLymphocyte ActivationMiceMice, TransgenicPolymorphism, GeneticStaphylococcus aureusStreptococcus pyogenesSuperantigensT-LymphocytesConceptsStreptococcal mitogenic exotoxin ZClass II moleculesHLA class II moleculesHLA-DQ6HLA-DQ8Transgenic miceBacterial superantigensImmune responseHLA class II transgenic miceHLA-DQ8 transgenic miceHuman leukocyte antigen (HLA) class II moleculesHLA class II allelesToxic shock syndrome toxin-1II transgenic miceSimilar clinical outcomesHLA-DQ polymorphismStreptococcal pyrogenic exotoxin AHLA class IIVivo immune responseHLA class II polymorphismClass II allelesPyrogenic exotoxin ASyndrome toxin-1Superantigen-mediated diseasesClass II polymorphism
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 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 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
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