Listeria monocytogenes spreads within the brain by actin-based intra-axonal migration

Henke, Diana; Rupp, Sebastian; Gaschen, Véronique; Stoffel, Michael Hubert; Frey, Joachim; Vandevelde, Marc; Oevermann, Anna (2015). Listeria monocytogenes spreads within the brain by actin-based intra-axonal migration. Infection and immunity, 83(6), pp. 2409-2419. American Society for Microbiology 10.1128/IAI.00316-15

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Listeria monocytogenes rhombencephalitis is a severe progressive disease despite a swift intrathecal immune response. Based on previous observations, we hypothesized that the disease progresses by intra-axonal spread within the central nervous system. To test this hypothesis, neuroanatomical mapping of lesions, immunofluorescence analysis, and electron microscopy were performed on brains of ruminants with naturally occurring rhombencephalitis. In addition, infection assays were performed in bovine brain cell cultures. Mapping of lesions revealed a consistent pattern with a preferential affection of certain nuclear areas and white matter tracts, indicating that Listeria monocytogenes spreads intra-axonally within the brain along interneuronal connections. These results were supported by immunofluorescence and ultrastructural data localizing Listeria monocytogenes inside axons and dendrites associated with networks of fibrillary structures consistent with actin tails. In vitro infection assays confirmed that bacteria were moving within axon-like processes by employing their actin tail machinery. Remarkably, in vivo, neutrophils invaded the axonal space and the axon itself, apparently by moving between split myelin lamellae of intact myelin sheaths. This intra-axonal invasion of neutrophils was associated with various stages of axonal degeneration and bacterial phagocytosis. Paradoxically, the ensuing adaxonal microabscesses appeared to provide new bacterial replication sites, thus supporting further bacterial spread. In conclusion, intra-axonal bacterial migration and possibly also the innate immune response play an important role in the intracerebral spread of the agent and hence the progression of listeric rhombencephalitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Anatomy
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Veterinary Bacteriology
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Henke, Diana; Rupp, Sebastian; Gaschen, Véronique; Stoffel, Michael Hubert; Frey, Joachim; Vandevelde, Marc and Oevermann, Anna

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0019-9567

Publisher:

American Society for Microbiology

Funders:

[4] Swiss National Science Foundation
[UNSPECIFIED] Ernst Frauchiger Stiftung

Language:

English

Submitter:

Miriam Francine Heinzelmann

Date Deposited:

18 Aug 2015 15:48

Last Modified:

22 Jan 2019 13:19

Publisher DOI:

10.1128/IAI.00316-15

PubMed ID:

25824833

BORIS DOI:

10.7892/boris.70589

URI:

https://boris.unibe.ch/id/eprint/70589

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