Neonatal susceptibility to meningitis results from the immaturity of epithelial barriers and gut microbiota
| Autor: | Lukas Hafner, Alessio Andronico, Marc Lecuit, Mariana Alonso, Simon Cauchemez, Pierre-Marie Lledo, Laetitia Travier |
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| Přispěvatelé: | Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Université Paris Cité (UPCité), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported financially by Institut Pasteur, the Microbes and Brain incentive program of Institut Pasteur, the Labex IBEID program, and Institut National de la Santé et de la Recherche Médicale. LH is supported by the Pasteur-Paris University (PPU) International PhD Program, funded by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 665807, and the 'Ecole Doctorale FIRE-Programme Bettencourt' of the CRI Paris., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Travier, Laetitia, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Permissiveness
Aging QH301-705.5 Neonatal meningitis Bacteremia [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Biology Gut flora [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] medicine.disease_cause Group B Meningitis Bacterial Streptococcus agalactiae neonatal [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] medicine [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Animals Intestinal Mucosa Biology (General) Wnt Signaling Pathway intestine choroid plexus Streptococcus microbiology Wnt signaling pathway meningitis Epithelial Cells Cell Biology biology.organism_classification medicine.disease [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology infection 3. Good health Gastrointestinal Microbiome Mice Inbred C57BL intestinal barrier Intercellular Junctions Animals Newborn Immunology Host-Pathogen Interactions [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Choroid plexus Disease Susceptibility [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Meningitis |
| Zdroj: | Cell Reports, Vol 35, Iss 13, Pp 109319-(2021) Cell Reports Cell Reports, 2021, 35 (13), pp.109319. ⟨10.1016/j.celrep.2021.109319⟩ Cell Reports, Elsevier Inc, 2021, 35 (13), pp.109319. ⟨10.1016/j.celrep.2021.109319⟩ |
| ISSN: | 2211-1247 |
| Popis: | We thank Dmitry Ershov from the Bioinformatics and Biostatistics Hub (Institut Pasteur, USR 3756CNRS) and the Image Analysis Hub for their help with the image and/or data analysis. We thank George M. Haustant and Thomas Cokelaer (Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA) for 16S sequencing. We thank Claire Poyart or the BM110 GBS strain and Ivan Gladwyn-Ng and Laurent Nguyen for helpful discussions and preliminary experiments. We thank the members of the Biology of Infection Unit for their support, Sylvain Levallois for critical reading, and Rémy Dailleux and Thifaine Pouillon for help, and the Institut Pasteur Animalerie Centrale and Gnotobiology Center.; International audience; Neonates are highly susceptible to bacterial meningitis as compared to children and adults. Group B streptococcus (GBS) is a major cause of neonatal meningitis. Neonatal meningitis can result from GBS intestinal colonization and translocation across the intestinal barrier (IB). Here, we show that the immaturity of the neonatal intestinal microbiota results in low resistance to GBS intestinal colonization and higher permissiveness of the gut vascular barrier. Additionally, the age-dependent but microbiota-independent Wnt activity in intestinal and choroid plexus (CP) epithelia results in a lower degree of cell-cell junctions’ polarization which favors bacterial translocation. This study reveals that neonatal susceptibility to GBS meningitis results from the age-dependent immaturity of the microbiota and developmental pathways associated with neonatal tissue growth, which concur to GBS gut colonization, systemic dissemination and neuroinvasion. Whereas the activation of developmental pathways is intrinsic to neonates, interventions aimed at maturing the microbiota may help prevent neonatal meningitis. |
| Databáze: | OpenAIRE |
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