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
Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice
Rajagopalan G, Krogman A, Chowdhary V. Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice. The Journal Of Immunology 2018, 200: 117.3-117.3. DOI: 10.4049/jimmunol.200.supp.117.3.Peer-Reviewed Original ResearchHLA-DR3 transgenic miceToxic shock syndromeIL-17Transgenic miceHLA-DR3Shock syndromeAdaptive T cell responsesStaphylococcal toxic shock syndromeIL-17 family membersT cell responsesRole of IFNStaphylococcus aureus infectionS. aureusNon-specific activationTh17 cellsSerum levelsHLA-DRMice succumbedSystemic elevationTh1 cellsAureus infectionTissue injuryT cellsInfectious agentsIFN
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‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model
Krogman A, Tilahun A, David CS, Chowdhary VR, Alexander MP, Rajagopalan G. HLA‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model. HLA 2016, 89: 20-28. PMID: 27863161, DOI: 10.1111/tan.12930.Peer-Reviewed Original ResearchToxic shock syndrome toxin-1Class II moleculesMHC class II moleculesHLA-DR allelesSyndrome toxin-1Transgenic miceImmune activationHuman leukocyte antigen (HLA) transgenic miceSpecific HLA class II allelesToxin 1Cytokine/chemokine responsesMajor histocompatibility complex (MHC) class II moleculesNonmenstrual toxic shock syndromeDifferent HLA-DR allelesHLA class II allelesStaphylococcal toxic shock syndrome toxin 1Severe organ pathologyDifferent HLA-DRB1 allelesMultiple immune parametersT cell expansionHLA-DRB1 allelesToxic shock syndromeTransgenic mouse modelOutcome of diseaseClass II allelesInfluence 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
Superantigen-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 aureus
2014
The 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 diseaseChronic 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
Linezolid 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 responseDetrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13)
Rajagopalan G, Tilahun A. Detrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13). The Journal Of Immunology 2012, 188: 164.13-164.13. DOI: 10.4049/jimmunol.188.supp.164.13.Peer-Reviewed Original ResearchToxic shock syndromeHLA-DR3 transgenic miceTreg numbersShock syndromeNon-menstrual toxic shock syndromeTransgenic miceCytokine/chemokine stormStaphylococcal toxic shock syndromeNumber of TregsMultiple organ failureStaphylococcal enterotoxin BChemokine stormMIP-1βOrgan failureMIP-1αUntreated groupSuperantigen exotoxinsDay 5Immune systemDay 0IL2CMiceEnterotoxin BStreptococcus pyogenesAdministrationThe 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 BHLA-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 mimicryHuman 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 strainsHLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation
Rajagopalan G, Tilahun A, Iijima K, David C, Kita H, Juhn Y. HLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation. HLA 2011, 77: 589-592. PMID: 21447115, DOI: 10.1111/j.1399-0039.2010.01617.x.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceHouse dust miteDust miteTransgenic miceTh2-predominant immune responseHouse dust mite extractInterleukin-13 levelsInflammatory cell countsBronchoalveolar lavage fluidTh2-type inflammationTransgenic mouse modelHLA-DR polymorphismAirway inflammationCytokine levelsBAL fluidEosinophil countHLA-DR3Childhood asthmaHLA-DR2Lavage fluidMite extractHLA-DRB1Immune responseInterleukin-4Mouse modelInterferon 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
Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice
Rajagopalan G, Epstein B, Lytle A, David C. Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice. The FASEB Journal 2008, 22: 848.11-848.11. DOI: 10.1096/fasebj.22.1_supplement.848.11.Peer-Reviewed Original ResearchToxic shock syndromeRegulatory T cellsHLA-DR3 transgenic miceT cellsTransgenic miceHLA class II transgenic miceDepletion of TregsII transgenic miceSerum cytokine levelsStaphylococcal enterotoxin BTreg cellsCytokine levelsIL-17Regulatory cellsSEB challengeIL-21IL-22Systemic exposureIL-6Shock syndromeIL-2IL-2RSplenic expressionTGF-b1Toxic shockHLA Class II Transgenic Mice Mimic Human Inflammatory Diseases
Mangalam A, Rajagopalan G, Taneja V, David C. HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases. Advances In Immunology 2008, 97: 65-147. PMID: 18501769, DOI: 10.1016/s0065-2776(08)00002-3.Peer-Reviewed Original ResearchConceptsHLA class II transgenic miceClass II moleculesII transgenic miceCommon autoimmune diseaseAutoimmune diseasesInflammatory diseasesTransgenic miceClass II genesDQ allelesHLA class II associationsInsulin-dependent diabetes mellitusHLA class II moleculesHLA transgenic miceCD4 T cellsClass II associationsHuman class II moleculesAutoimmune disease developmentToxic shock syndromeT cell repertoireHLA class II genesHuman inflammatory diseasesSimilar antigenic epitopesMHC class II genesAutoimmune myocarditisDiabetes mellitus
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 ResearchConceptsStreptococcal 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 polymorphismDelineating the Roles of CD4+ and CD8+ T Cell Subsets in the Pathogenesis of Spontaneous Autoimmune Diabetes Using HLA-DQ8 Transgenic Mice
Rajagopalan G, Mangalam A, Kudva Y, David C. Delineating the Roles of CD4+ and CD8+ T Cell Subsets in the Pathogenesis of Spontaneous Autoimmune Diabetes Using HLA-DQ8 Transgenic Mice. Clinical Immunology 2007, 123: s71. DOI: 10.1016/j.clim.2007.03.379.Peer-Reviewed Original Research