2023
The maternal gut microbiome in pregnancy: implications for the developing immune system
Koren O, Konnikova L, Brodin P, Mysorekar I, Collado M. The maternal gut microbiome in pregnancy: implications for the developing immune system. Nature Reviews Gastroenterology & Hepatology 2023, 21: 35-45. PMID: 38097774, DOI: 10.1038/s41575-023-00864-2.Peer-Reviewed Original ResearchQuestioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
Kennedy K, de Goffau M, Perez-Muñoz M, Arrieta M, Bäckhed F, Bork P, Braun T, Bushman F, Dore J, de Vos W, Earl A, Eisen J, Elovitz M, Ganal-Vonarburg S, Gänzle M, Garrett W, Hall L, Hornef M, Huttenhower C, Konnikova L, Lebeer S, Macpherson A, Massey R, McHardy A, Koren O, Lawley T, Ley R, O’Mahony L, O’Toole P, Pamer E, Parkhill J, Raes J, Rattei T, Salonen A, Segal E, Segata N, Shanahan F, Sloboda D, Smith G, Sokol H, Spector T, Surette M, Tannock G, Walker A, Yassour M, Walter J. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature 2023, 613: 639-649. PMID: 36697862, PMCID: PMC11333990, DOI: 10.1038/s41586-022-05546-8.Peer-Reviewed Original ResearchConceptsMicrobial populationsHuman immune developmentMicrobial ecologyReproductive biologyMicrobial communitiesLow biomass environmentsMicrobial signalsMicrobial studiesDNA sequencingMicrobiome studiesDNA extractionMicrobial analysisClinical microbiologyMechanistic conceptsCautionary exampleImmune developmentRecent studiesHuman fetusesFetal tissuesMammalsGnotobiologyEcologyMicrobiologyFetal microbiomeBiology
2022
Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation
Wang M, Silva T, Toothaker JM, McCourt BT, Shugrue C, Desir G, Gorelick F, Konnikova L. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation. Scientific Reports 2022, 12: 4953. PMID: 35322081, PMCID: PMC8943056, DOI: 10.1038/s41598-022-08817-6.Peer-Reviewed Original ResearchConceptsPlacental tissuePlacental villiHofbauer cellsPlacental developmentEndogenous productionAnti-inflammatory milieuPotential roleHuman placental tissueFull-term placentaPlacental factorsFetal interfaceDecidual samplesPlacental functionChorionic plateImmunoreactive cellsPlacental samplesHuman gestationRenalaseBulk RNA sequencingHuman placentaPlacentaQuantification of immunohistochemistryProtein levelsTrophoblastTransmission of nutrientsImmune landscape of human placental villi using single-cell analysis
Toothaker JM, Olaloye O, McCourt BT, McCourt CC, Silva TN, Case RM, Liu P, Yimlamai D, Tseng G, Konnikova L. Immune landscape of human placental villi using single-cell analysis. Development 2022, 149 PMID: 35050308, PMCID: PMC8935213, DOI: 10.1242/dev.200013.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticB-LymphocytesB7-H1 AntigenChorionic VilliFemaleFetusFlow CytometryHLA-DR AntigensHumansKiller Cells, NaturalLeukocyte Common AntigensLymphocyte ActivationMacrophagesMemory T CellsPlacentaPregnancyPregnancy Trimester, SecondReceptors, Cell SurfaceReceptors, ChemokineSingle-Cell AnalysisT-LymphocytesConceptsT cellsHuman placental villiPlacental villiImmune systemFetal immune systemMaternal immune systemFetal immune cellsAdult T-cellT cell receptor stimulationCell receptor stimulationHealthy pregnancyImmune landscapeMemory phenotypeImmune cellsFetal organsEnhanced proliferative capacityReceptor stimulationMultiple subtypesPV tissueComplex immune systemImaging modalitiesMass cytometryProliferative capacityMaternal mechanismsRecent reports
2021
Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activationSmall intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia
Konnikova L, Robinson TO, Owings AH, Shirley JF, Davis E, Tang Y, Wall S, Li J, Hasan MH, Gharaibeh RZ, Mendoza Alvarez LB, Ryan LK, Doty A, Chovanec JF, O'Connell MP, Grunes DE, Daley WP, Mayer E, Chang L, Liu J, Snapper SB, Milner JD, Glover SC, Lyons JJ. Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia. Journal Of Allergy And Clinical Immunology 2021, 148: 813-821.e7. PMID: 33865872, PMCID: PMC9017395, DOI: 10.1016/j.jaci.2021.04.004.Peer-Reviewed Original ResearchConceptsClass-switched memory B cellsMemory B cellsB cellsSyndrome cohortCell pyroptosisFunctional GI diseasesQuiescent Crohn's diseaseSmall intestinal immunopathologySubclinical intestinal inflammationFunctional gastrointestinal symptomsMast cell numbersTissue mast cellsExpression of CD203cBasal serum tryptaseElevated basal serum tryptaseIntestinal immunopathologyGastrointestinal symptomsImmunologic findingsIntestinal inflammationCrohn's diseaseHLA-DRSmall bowelGI diseaseIgG reactiveImmunologic characteristics
2020
In utero human intestine harbors unique metabolomic features including bacterial metabolites
Li Y, Toothaker JM, Ben-Simon S, Ozeri L, Schweitzer R, McCourt BT, McCourt CC, Werner L, Snapper SB, Shouval DS, Khatib S, Koren O, Agnihorti S, Tseng G, Konnikova L. In utero human intestine harbors unique metabolomic features including bacterial metabolites. JCI Insight 2020, 5: e138751. PMID: 33001863, PMCID: PMC7710283, DOI: 10.1172/jci.insight.138751.Peer-Reviewed Original ResearchConceptsFetal immune systemIntestinal barrier integrityMicrobial-associated metabolitesHost-derived metabolitesBacterial DNAIntestinal immunityMaternal microbiomeIntestinal functionImmune regulationGastrointestinal tractIntestinal microbiomeFetal intestineBarrier integrityImmune systemHuman intestinal samplesIntestinal samplesIntestinal profileMicrobial encountersMetabolomic featuresBacterial metabolitesUteroNutrient metabolismMetabolitesRecent studiesMicrobiomeImmune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation
Toothaker JM, Presicce P, Cappelletti M, Stras SF, McCourt CC, Chougnet CA, Kallapur SG, Konnikova L. Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation. Frontiers In Immunology 2020, 11: 866. PMID: 32528468, PMCID: PMC7256198, DOI: 10.3389/fimmu.2020.00866.Peer-Reviewed Original ResearchConceptsFetal-maternal interfaceIntra-amniotic inflammationImmune cellsVillous placentaT cellsPlacental villiNatural killerTumor necrosis factor alphaAbundance of neutrophilsIA LPS exposureCD8 T cellsMemory T cellsAntigen-presenting cellsRhesus macaque modelNecrosis factor alphaDistinct immunological profilePotential therapeutic targetTNFα blockadeLPS exposureSignificant morbidityMacaque modelProinflammatory cytokinesImmunological profileFactor alphaImmunological responseThe Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source
Wen L, Javed TA, Dobbs AK, Brown R, Niu M, Li L, Khalid A, Barakat M, Xiao X, Yimlamai D, Konnikova L, Yu M, Byersdorfer CA, Husain SZ. The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source. Gastroenterology 2020, 159: 1036-1050.e8. PMID: 32445858, PMCID: PMC7502475, DOI: 10.1053/j.gastro.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAcute Lung InjuryAnimalsBone Marrow CellsCalcineurinCalcineurin InhibitorsCalcium-Binding ProteinsCells, CulturedCeruletideCytokinesDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicMuscle ProteinsNeutrophilsNFATC Transcription FactorsPancreasPancreatitisPrimary Cell CultureConceptsAdministration of caeruleinLocal pancreatic inflammationBiliopancreatic ductPancreas-specific deletionLung inflammationPancreatic inflammationAcute pancreatitisControl miceNeutrophil chemotaxisProtective effectHematopoietic-specific deletionPancreatic acinar cell necrosisPrevention of pancreatitisLevels of cytokinesAcinar cell necrosisSwiss Webster miceActivated T cellsAdeno-associated virus vectorPrimary pancreatic acinar cellsReactive oxygen species productionNFAT-luciferaseSevere pancreatitisCalcineurin inhibitorsNeutrophil expressionPancreatic acinar cellsSingle-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease
Mitsialis V, Wall S, Liu P, Ordovas-Montanes J, Parmet T, Vukovic M, Spencer D, Field M, McCourt C, Toothaker J, Bousvaros A, Center B, Ballal S, Bonilla S, Fawaz R, Fishman L, Flores A, Fox V, Grover A, Higuchi L, Huh S, Kahn S, Lee C, Mobassaleh M, Ouahed J, Pleskow R, Regan B, Rufo P, Sabharwal S, Silverstein J, Verhave M, Wolf A, Zimmerman L, Zitomersky N, Center B, Allegretti J, De Silva P, Friedman S, Hamilton M, Korzenik J, Makrauer F, Norton B, Winter R, Shalek A, Kean L, Horwitz B, Goldsmith J, Tseng G, Snapper S, Konnikova L. Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease. Gastroenterology 2020, 159: 591-608.e10. PMID: 32428507, PMCID: PMC8166295, DOI: 10.1053/j.gastro.2020.04.074.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseasePeripheral blood mononuclear cellsActive Crohn's diseaseBlood mononuclear cellsColonic mucosa samplesActive ulcerative colitisPlasmacytoid dendritic cellsInnate lymphoid cellsUlcerative colitisCrohn's diseaseDendritic cellsImmune cell populationsRegulatory cellsMononuclear cellsT cellsMucosa samplesBlood samplesLymphoid cellsGroup 1 innate lymphoid cellsType 3 innate lymphoid cellsEffector memory T cellsCell populationsInactive ulcerative colitisInactive Crohn's diseaseMemory T cellsRole of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review
Olaloye O, Swatski M, Konnikova L. Role of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review. Nutrients 2020, 12: 1347. PMID: 32397283, PMCID: PMC7284579, DOI: 10.3390/nu12051347.Peer-Reviewed Original ResearchMeSH KeywordsEatingEnteral NutritionFeeding MethodsFemaleHumansInfant, Extremely Low Birth WeightInfant, NewbornIntestinal PerforationLength of StayMaleNeurodevelopmental DisordersNutritional Physiological PhenomenaParenteral NutritionPostoperative CarePostoperative ComplicationsSpontaneous PerforationTime FactorsConceptsSpontaneous intestinal perforationIncidence of SIPRole of nutritionEnteral nutritionIntestinal perforationFeeding practicesSystematic reviewEarly enteral nutritionFull enteral feedsPost-operative nutritionLow birthweight infantsLength of stayHistorical control studySearch of PubMedDays of lifeMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsRelevant search termsELBW infantsNutrition initiationCohort studyDevastating complicationParenteral nutritionSecondary outcomesEnteral feeds
2019
Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development
Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL, McCourt CC, Lee YN, Rechavi E, Shouval DS, Konnikova L. Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development. Developmental Cell 2019, 51: 357-373.e5. PMID: 31607651, DOI: 10.1016/j.devcel.2019.09.008.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell ProliferationClone CellsCytokinesFemaleFetal DevelopmentFetusHumansImmune SystemImmunity, MucosalImmunologic MemoryImmunophenotypingInfant, NewbornIntestinesPregnancyPregnancy Trimester, SecondReceptors, Antigen, B-CellReceptors, Antigen, T-CellT-LymphocytesV(D)J RecombinationConceptsInnate lymphoid cellsGestational ageIntestinal immunityDendritic cellsB cellsHuman intestinal immune systemAdaptive immune landscapeIntestinal immune systemNatural killer cellsWeeks gestational ageTransitional B cellsB cell maturityT cell receptorComplex innateImmune atlasEarly life developmentImmune landscapeKiller cellsTCR repertoireLymphoid cellsFetal developmentImmune systemInnate immunityCell receptorMass cytometry
2018
Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy
Kotlarz D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Conca R, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Strømme P, Klein C. Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nature Genetics 2018, 50: 344-348. PMID: 29483653, PMCID: PMC6309869, DOI: 10.1038/s41588-018-0063-6.Peer-Reviewed Original ResearchConceptsInfantile inflammatory bowel diseaseInflammatory bowel diseaseTGF-β1Bowel diseaseSevere inflammatory bowel diseaseCentral nervous system diseaseNervous system diseasesRole of TGFPosterior leukoencephalopathyIntestinal immunityBrain atrophySystem diseasesTGFB1 geneBiallelic lossImpaired secretionGrowth factorTGF-β familyDiseaseTGF-β1 deficiencyNonredundant roleFunction mutationsPrototypic memberLeukoencephalopathyAtrophyEpilepsy
2017
An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning
Sallis BF, Erkert L, Moñino-Romero S, Acar U, Wu R, Konnikova L, Lexmond WS, Hamilton MJ, Dunn WA, Szepfalusi Z, Vanderhoof JA, Snapper SB, Turner JR, Goldsmith JD, Spencer LA, Nurko S, Fiebiger E. An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning. Journal Of Allergy And Clinical Immunology 2017, 141: 1354-1364.e9. PMID: 29273402, PMCID: PMC6425755, DOI: 10.1016/j.jaci.2017.11.027.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsChildChild, PreschoolDecision Support Systems, ClinicalDecision Support TechniquesEosinophilic EsophagitisFactor Analysis, StatisticalFemaleGenetic MarkersHumansImmunohistochemistryInfantMachine LearningMaleRegistriesRNA, MessengerSensitivity and SpecificitySingle-Blind MethodConceptsAllergic statusEosinophilic esophagitisPatient's allergic statusGastroesophageal reflux diseaseBiopsies of patientsEpsilon germ-line transcriptsEoE patientsReflux diseaseAllergic inflammationIgE productionSerum IgEEquivocal patientsPatient subpopulationsDiagnostic evaluationIndividualized therapyEquivocal casesPrimary analysisPatient careGerm-line transcriptsEoEPatientsDiagnostic precisionEsophagitisScoresTherapyEnhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD
Shouval DS, Konnikova L, Griffith AE, Wall SM, Biswas A, Werner L, Nunberg M, Kammermeier J, Goettel JA, Anand R, Chen H, Weiss B, Li J, Loizides A, Yerushalmi B, Yanagi T, Beier R, Conklin LS, Ebens CL, Santos FGMS, Sherlock M, Goldsmith JD, Kotlarz D, Glover SC, Shah N, Bousvaros A, Uhlig HH, Muise AM, Klein C, Snapper SB. Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD. Inflammatory Bowel Diseases 2017, 23: 1950-1961. PMID: 29023267, DOI: 10.1097/mib.0000000000001270.Peer-Reviewed Original ResearchConceptsT cell proliferationDeficient patientsTh17 cellsReceptor deficiencySevere infantile-onset inflammatory bowel diseaseInfantile-onset inflammatory bowel diseaseAdaptive immune cell functionsCD4 T cell functionCD4 T cell proliferationCD4 T cell subsetsHematopoietic stem cell transplantationPeripheral blood mononuclear cellsNaive T cell proliferationSuppression of TregsGeneration of TregsInflammatory bowel diseaseRegulatory T cellsStem cell transplantationT cell subsetsBlood mononuclear cellsImmune cell defectsAnti-inflammatory macrophagesT cell functionImmune cell functionReal-time polymerase chain reaction
2012
The Role of Pulmonary Follow-up in Reducing Health Care Utilization in Infants With Bronchopulmonary Dysplasia
Rhein LM, Konnikova L, McGeachey A, Pruchniewski M, Smith VC. The Role of Pulmonary Follow-up in Reducing Health Care Utilization in Infants With Bronchopulmonary Dysplasia. Clinical Pediatrics 2012, 51: 645-650. PMID: 22492835, DOI: 10.1177/0009922812439242.Peer-Reviewed Original ResearchConceptsRate of rehospitalizationHealth care utilizationPreterm infantsBronchopulmonary dysplasiaED visitsEmergency departmentCare utilizationNeonatal intensive care unitMore supplemental oxygenRole of PulmonaryRetrospective cohort studyIntensive care unitSevere lung diseaseTime of dischargeChildren's Hospital BostonRate of visitsElectronic medical recordsExpected higher rateNeurodevelopmental followCohort studyWeeks' gestationCare unitOutpatient visitsRespiratory causesSupplemental oxygen