Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood

ABSTRACT Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bac...

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Autores principales:	Taylor E. Senay, Jessica L. Ferrell, Filip G. Garrett, Taylor M. Albrecht, Jooyoung Cho, Katie L. Alexander, Tanya Myers-Morales, Olivia F. Grothaus, Sarah E. F. D’Orazio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Listeria monocytogenes foodborne infection mouse models Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2e391544e48a44ed80e087d995547c5f
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spelling	oai:doaj.org-article:2e391544e48a44ed80e087d995547c5f2021-11-15T15:30:58ZNeurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood10.1128/mSphere.00871-202379-5042https://doaj.org/article/2e391544e48a44ed80e087d995547c5f2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00871-20https://doaj.org/toc/2379-5042ABSTRACT Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes. Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem. IMPORTANCE Progress in understanding the two naturally occurring central nervous system (CNS) manifestations of listeriosis (meningitis/meningoencephalitis and rhombencephalitis) has been limited by the lack of small animal models that can readily distinguish between these distinct infections. We report here that certain neurotropic strains of Listeria monocytogenes can spread to the brains of young otherwise healthy mice and cause neurological deficits without causing a fatal bacteremia. The novel strains described here fall within phylogenetic lineage III, a small collection of L. monocytogenes isolates that have not been well characterized to date. The animal model reported here mimics many features of human rhombencephalitis and will be useful for studying the mechanisms that allow L. monocytogenes to disseminate to the brain stem following natural foodborne transmission.Taylor E. SenayJessica L. FerrellFilip G. GarrettTaylor M. AlbrechtJooyoung ChoKatie L. AlexanderTanya Myers-MoralesOlivia F. GrothausSarah E. F. D’OrazioAmerican Society for MicrobiologyarticleListeria monocytogenesfoodborne infectionmouse modelsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Listeria monocytogenes foodborne infection mouse models Microbiology QR1-502
spellingShingle	Listeria monocytogenes foodborne infection mouse models Microbiology QR1-502 Taylor E. Senay Jessica L. Ferrell Filip G. Garrett Taylor M. Albrecht Jooyoung Cho Katie L. Alexander Tanya Myers-Morales Olivia F. Grothaus Sarah E. F. D’Orazio Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
description	ABSTRACT Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes. Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem. IMPORTANCE Progress in understanding the two naturally occurring central nervous system (CNS) manifestations of listeriosis (meningitis/meningoencephalitis and rhombencephalitis) has been limited by the lack of small animal models that can readily distinguish between these distinct infections. We report here that certain neurotropic strains of Listeria monocytogenes can spread to the brains of young otherwise healthy mice and cause neurological deficits without causing a fatal bacteremia. The novel strains described here fall within phylogenetic lineage III, a small collection of L. monocytogenes isolates that have not been well characterized to date. The animal model reported here mimics many features of human rhombencephalitis and will be useful for studying the mechanisms that allow L. monocytogenes to disseminate to the brain stem following natural foodborne transmission.
format	article
author	Taylor E. Senay Jessica L. Ferrell Filip G. Garrett Taylor M. Albrecht Jooyoung Cho Katie L. Alexander Tanya Myers-Morales Olivia F. Grothaus Sarah E. F. D’Orazio
author_facet	Taylor E. Senay Jessica L. Ferrell Filip G. Garrett Taylor M. Albrecht Jooyoung Cho Katie L. Alexander Tanya Myers-Morales Olivia F. Grothaus Sarah E. F. D’Orazio
author_sort	Taylor E. Senay
title	Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
title_short	Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
title_full	Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
title_fullStr	Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
title_full_unstemmed	Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood
title_sort	neurotropic lineage iii strains of <named-content content-type="genus-species">listeria monocytogenes</named-content> disseminate to the brain without reaching high titer in the blood
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/2e391544e48a44ed80e087d995547c5f
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Neurotropic Lineage III Strains of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Disseminate to the Brain without Reaching High Titer in the Blood

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