The olfactory epithelium as a port of entry in neonatal neurolisteriosis

Bacterial infections of the central nervous system (CNS) remain a major cause of mortality in the neonatal population. Commonly used parenteral infection models, however, do not reflect the early course of the disease leaving this critical step of the pathogenesis largely unexplored. Here, we analyz...

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Autores principales: Pägelow, Dennis, Chhatbar, Chintan, Beineke, Andreas, Liu, Xiaokun, Nerlich, Andreas, van Vorst, Kira, Rohde, Manfred, Kalinke, Ulrich, Förster, Reinhold, Halle, Stephan, Valentin-Weigand, Peter, Hornef, Mathias W., Fulde, Marcus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189187/
https://www.ncbi.nlm.nih.gov/pubmed/30323282
http://dx.doi.org/10.1038/s41467-018-06668-2
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author Pägelow, Dennis
Chhatbar, Chintan
Beineke, Andreas
Liu, Xiaokun
Nerlich, Andreas
van Vorst, Kira
Rohde, Manfred
Kalinke, Ulrich
Förster, Reinhold
Halle, Stephan
Valentin-Weigand, Peter
Hornef, Mathias W.
Fulde, Marcus
author_facet Pägelow, Dennis
Chhatbar, Chintan
Beineke, Andreas
Liu, Xiaokun
Nerlich, Andreas
van Vorst, Kira
Rohde, Manfred
Kalinke, Ulrich
Förster, Reinhold
Halle, Stephan
Valentin-Weigand, Peter
Hornef, Mathias W.
Fulde, Marcus
author_sort Pägelow, Dennis
collection PubMed
description Bacterial infections of the central nervous system (CNS) remain a major cause of mortality in the neonatal population. Commonly used parenteral infection models, however, do not reflect the early course of the disease leaving this critical step of the pathogenesis largely unexplored. Here, we analyzed nasal exposure of 1-day-old newborn mice to Listeria monocytogenes (Lm). We found that nasal, but not intragastric administration, led to early CNS infection in neonate mice. In particular, upon bacterial invasion of the olfactory epithelium, Lm subsequently spread along the sensory neurons entering the brain tissue at the cribriform plate and causing a significant influx of monocytes and neutrophils. CNS infection required listeriolysin for penetration of the olfactory epithelium and ActA, a mediator of intracellular mobility, for translocation into the brain tissue. Taken together, we propose an alternative port of entry and route of infection for neonatal neurolisteriosis and present a novel infection model to mimic the clinical features of late-onset disease in human neonates.
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spelling pubmed-61891872018-10-17 The olfactory epithelium as a port of entry in neonatal neurolisteriosis Pägelow, Dennis Chhatbar, Chintan Beineke, Andreas Liu, Xiaokun Nerlich, Andreas van Vorst, Kira Rohde, Manfred Kalinke, Ulrich Förster, Reinhold Halle, Stephan Valentin-Weigand, Peter Hornef, Mathias W. Fulde, Marcus Nat Commun Article Bacterial infections of the central nervous system (CNS) remain a major cause of mortality in the neonatal population. Commonly used parenteral infection models, however, do not reflect the early course of the disease leaving this critical step of the pathogenesis largely unexplored. Here, we analyzed nasal exposure of 1-day-old newborn mice to Listeria monocytogenes (Lm). We found that nasal, but not intragastric administration, led to early CNS infection in neonate mice. In particular, upon bacterial invasion of the olfactory epithelium, Lm subsequently spread along the sensory neurons entering the brain tissue at the cribriform plate and causing a significant influx of monocytes and neutrophils. CNS infection required listeriolysin for penetration of the olfactory epithelium and ActA, a mediator of intracellular mobility, for translocation into the brain tissue. Taken together, we propose an alternative port of entry and route of infection for neonatal neurolisteriosis and present a novel infection model to mimic the clinical features of late-onset disease in human neonates. Nature Publishing Group UK 2018-10-15 /pmc/articles/PMC6189187/ /pubmed/30323282 http://dx.doi.org/10.1038/s41467-018-06668-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pägelow, Dennis
Chhatbar, Chintan
Beineke, Andreas
Liu, Xiaokun
Nerlich, Andreas
van Vorst, Kira
Rohde, Manfred
Kalinke, Ulrich
Förster, Reinhold
Halle, Stephan
Valentin-Weigand, Peter
Hornef, Mathias W.
Fulde, Marcus
The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title_full The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title_fullStr The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title_full_unstemmed The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title_short The olfactory epithelium as a port of entry in neonatal neurolisteriosis
title_sort olfactory epithelium as a port of entry in neonatal neurolisteriosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189187/
https://www.ncbi.nlm.nih.gov/pubmed/30323282
http://dx.doi.org/10.1038/s41467-018-06668-2
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