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 activation
2020
Immune 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 response
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