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
2019
Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality
Park K, Greenwood-Quaintance K, Cunningham S, Rajagopalan G, Chia N, Jeraldo P, Mandrekar J, Patel R. Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality. Microbial Pathogenesis 2019, 133: 103543. PMID: 31102653, DOI: 10.1016/j.micpath.2019.103543.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAnimalsBacteremiaBacterial AdhesionBase SequenceCell ProliferationDrug Resistance, BacterialFemaleHLA-DR3 AntigenHumansImmune EvasionMaleMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicMiddle AgedMinnesotaPolymerase Chain ReactionStaphylococcal InfectionsStaphylococcus aureusSuperantigensVirulenceVirulence FactorsConceptsMethicillin-susceptible S. aureusS. aureus bacteremiaAureus bacteremiaMedical CenterHLA-DR3 transgenic miceStaphylococcus aureus bacteremiaMinnesota Medical CenterLarge medical centerImmune evasion genesVirulence genesVirulence gene profilesNumber of deathsClinical dataClinical valueTransgenic miceClinical practiceIndividual PCR assaysWhole-genome sequencing analysisMortalitySAg genesSurvivorsLack of correlationBacteremiaWGS analysisFunctional assays
2018
Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease
Miyabe K, Zen Y, Cornell LD, Rajagopalan G, Chowdhary VR, Roberts LR, Chari ST. Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease. Gastroenterology 2018, 155: 990-1003.e1. PMID: 30012334, DOI: 10.1053/j.gastro.2018.06.082.Peer-Reviewed Original ResearchConceptsIgG4-RDPlasma cellsExtra-intestinal manifestationsHuman IgG4-RDSimilar immune reactionsRelapsing-remitting courseDense lymphoplasmacytic infiltrateTiters of autoantibodiesMulti-organ diseasePermanent organ damageObliterative phlebitisStoriform fibrosisAutoimmune etiologyMetachronous lesionsPrimary therapyExcellent prognosisLymph nodesLymphoplasmacytic infiltrateSerum levelsOrgan damageSerum IgG4Bile ductAutoimmune diseasesTypical presentationInflammatory response
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
Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model
Sheen Y, Rajagopalan G, Snapper C, Kita H, Wi C, Umaretiya P, Juhn Y. Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. HLA 2016, 88: 25-34. PMID: 27506953, PMCID: PMC6326101, DOI: 10.1111/tan.12851.Peer-Reviewed Original ResearchConceptsHouse dust miteHumoral immune responseAnti-pneumococcal polysaccharideHLA-DR polymorphismImmune responseHDM sensitizationIntact pneumococciHLA-DR3IgG responsesSerum titersTransgenic miceIntranasal house dust miteAnti-phosphorylcholine IgMHLA-DR3 miceLower humoral immune responseHalf of miceTransgenic mouse modelAllergic sensitizationPneumococcal diseaseIgM responseDR3 miceDust mitePneumococcal polysaccharideMouse modelA-IgG
2015
Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice
Krogman AL, Chowdhary V, Rajagopalan G. Mini-Osmotic Pump Infusion Model to Investigate the Systemic Effects of Chronic Continuous Exposure to Staphylococcal Superantigen in Mice. Methods In Molecular Biology 2015, 1396: 109-114. PMID: 26676041, PMCID: PMC4882905, DOI: 10.1007/978-1-4939-3344-0_9.Peer-Reviewed Original ResearchConceptsStaphylococcal superantigensMini-osmotic pumpsChronic continuous exposureSpectrum of diseaseSystemic effectsAcute exposureChronic exposureImmune systemRecurrent exposureSuperantigensContinuous exposureRobust activationS. aureusStaphylococcus aureusInfusion modelExposureAureusSafe wayDiseaseMiceSuperantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, Krogman A, David C, Pritt B, Patel R, Rajagopalan G. Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model. Toxins 2015, 7: 5308-5319. PMID: 26670252, PMCID: PMC4690136, DOI: 10.3390/toxins7124886.Peer-Reviewed Original ResearchConceptsSystemic immune activationImmune activationT cellsS. aureusSerum IL-17 levelsSystemic immunologic effectsIL-17 levelsSpleens of miceWound infection modelImmunologic effectsInflammatory changesHLA-DR3Wound infectionCommon causeTransgenic miceUninfected woundsDay 8Immune systemClinical implicationsInfection modelMiceSkin woundsWoundsMicrobial challengeStaphylococcus aureusA Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus
Chowdhary VR, Dai C, Tilahun AY, Hanson JA, Smart MK, Grande JP, Rajagopalan G, Fu SM, David CS. A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus. The Journal Of Immunology 2015, 195: 4660-4667. PMID: 26475924, PMCID: PMC5292932, DOI: 10.4049/jimmunol.1501073.Peer-Reviewed Original ResearchConceptsHLA-DR3NZM2328 miceClass IIMouse modelEndogenous MHC class IIAnti-dsDNA titersWire-loop lesionsSystemic lupus erythematosusSpecific HLA allelesMHC class IITransgenic mouse modelAnti-Sm AbsLupus erythematosusSevere proteinuriaAutoimmune responseHLA-DR2Lymphoid aggregatesAntibody responseHLA-DR3 moleculesHistological scoresT cellsImmune responseSpontaneous lupusHLA allelesHuman studiesSuperantigens 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
Superantigens in Staphylococcus aureus isolated from prosthetic joint infection
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, David C, Mandrekar J, Patel R, Rajagopalan G. Superantigens in Staphylococcus aureus isolated from prosthetic joint infection. Diagnostic Microbiology And Infectious Disease 2014, 81: 201-207. PMID: 25619753, PMCID: PMC4336809, DOI: 10.1016/j.diagmicrobio.2014.11.007.Peer-Reviewed Original ResearchSystemic 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 diseaseSuperantigen profiling of Staphylococcus aureus infective endocarditis isolates
Chung J, Karau M, Greenwood-Quaintance K, Ballard A, Tilahun A, Khaleghi S, David C, Patel R, Rajagopalan G. Superantigen profiling of Staphylococcus aureus infective endocarditis isolates. Diagnostic Microbiology And Infectious Disease 2014, 79: 119-124. PMID: 24745820, PMCID: PMC4031024, DOI: 10.1016/j.diagmicrobio.2014.03.009.Peer-Reviewed Original ResearchConceptsSuperantigen genesSplenocyte proliferationS. aureusStaphylococcus aureus infective endocarditisMethicillin-susceptible S. aureusMethicillin-resistant S. aureusInfective endocarditis casesEnzyme-linked immunosorbent assayStaphylococcal enterotoxin AInfective endocarditisEndocarditis casesSuperantigen productionMouse splenocyte proliferationPCR-positive isolatesTSST-1EndocarditisImmunosorbent assayEnterotoxin AStaphylococcus aureusAureusProliferationIsolatesMortalityGenes
2013
Low Incidence of Spontaneous Type 1 Diabetes in Non-Obese Diabetic Mice Raised on Gluten-Free Diets Is Associated with Changes in the Intestinal Microbiome
Marietta E, Gomez A, Yeoman C, Tilahun A, Clark C, Luckey D, Murray J, White B, Kudva Y, Rajagopalan G. Low Incidence of Spontaneous Type 1 Diabetes in Non-Obese Diabetic Mice Raised on Gluten-Free Diets Is Associated with Changes in the Intestinal Microbiome. PLOS ONE 2013, 8: e78687. PMID: 24236037, PMCID: PMC3827256, DOI: 10.1371/journal.pone.0078687.Peer-Reviewed Original ResearchConceptsGluten-free dietNon-obese diabetic (NOD) miceAnti-diabetogenic effectsIncidence of hyperglycemiaNOD miceType 1 diabetesIntestinal microbiomeDietary glutenDiabetic miceSpontaneous type 1 diabetesAkkermansia speciesIncidence of diabetesIncidence of T1DIncidence of T1D.Blood glucose levelsIntestinal microbiome compositionLower incidenceGlucose levelsHigh incidenceAnimal studiesGut microfloraGut microbiomeHyperglycemiaIncidenceMice
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 roleLinezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice
Karau M, Tilahun A, Schmidt S, Clark C, Patel R, Rajagopalan G. Linezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice. Antimicrobial Agents And Chemotherapy 2012, 56: 5401-5405. PMID: 22850509, PMCID: PMC3457354, DOI: 10.1128/aac.01080-12.Peer-Reviewed Original ResearchConceptsHLA class II transgenic miceTransgenic miceDR3 transgenic miceII transgenic miceHuman leukocyte antigenS. aureusC57BL/6 miceLeukocyte antigenStaphylococcus aureus virulenceExperimental pneumoniaImmune systemSuperantigensPneumoniaAureus virulenceMiceBacterial protein synthesis inhibitorsProtein synthesis inhibitorStaphylococcus aureusLinezolidPotent activatorSynthesis inhibitorVancomycinAureusGreater protectionSuperior responseIs HOT a Cool Treatment for Type 1 Diabetes?
Rajagopalan G, Kudva Y, David C. Is HOT a Cool Treatment for Type 1 Diabetes? Diabetes 2012, 61: 1664-1666. PMID: 22723274, PMCID: PMC3379652, DOI: 10.2337/db12-0527.Peer-Reviewed Original ResearchThe 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 B