Influence of perineurial cells and Toll-like receptors 2 and 9 on Herpes simplex type 1 entry to the central nervous system in rat encephalitis

Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whis...

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Bibliographic Details
Published in:PloS one 2010-08, Vol.5 (8), p.e12350-e12350
Main Authors: Bereczky-Veress, Biborka, Abdelmagid, Nada, Piehl, Fredrik, Bergström, Tomas, Olsson, Tomas, Sköldenberg, Birgit, Diez, Margarita
Format: Article
Language:English
Subjects:
activation
Animals
Antigens
Brain stem
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - virology
Cell adhesion & migration
Cell growth
Central nervous system
Central Nervous System - metabolism
Central Nervous System - pathology
Central Nervous System - virology
Coding
Comparative analysis
deficiency
Dendritic Cells - immunology
Dendritic Cells - virology
Encephalitis
Encephalitis, Viral - immunology
Encephalitis, Viral - metabolism
Encephalitis, Viral - virology
expression
fibrillary acidic protein
Ganglia
Gene expression
Gene Expression Regulation - immunology
Genetic code
Genetics and Genomics/Gene Expression
Genetics and Genomics/Genetics of Disease
Genetics and Genomics/Genetics of the Immune System
Health aspects
Herpes simplex
Herpes simplex virus 1
Herpes viruses
Herpesvirus 1, Human - physiology
Histocompatibility Antigens Class I - metabolism
Histocompatibility Antigens Class II - metabolism
Hospitals
Humans
Immune system
Immunity, Innate
Immunohistochemistry
Immunology
Immunology/Genetics of the Immune System
Immunology/Immune Response
Immunology/Immunity to Infections
Immunology/Innate Immunity
Infections
Infectious diseases
Infectious Diseases/Infectious Diseases of the Nervous System
Infectious Diseases/Viral Infections
Inflammation Mediators - metabolism
Ischemia
Killer Cells, Natural - immunology
Killer Cells, Natural - virology
Kinetics
Macrophages - immunology
Macrophages - virology
Male
MEDICAL AND HEALTH SCIENCES
MEDICIN OCH HÄLSOVETENSKAP
Microscopy
Molecular modelling
molecules
Morbidity
Neurosciences
Pathology/Cellular Pathology
Peripheral Nerves - metabolism
Peripheral Nerves - pathology
Peripheral Nerves - virology
Phagocytes
proliferation
Proteins
Rare diseases
Rats
Receptors
recognition
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Schwann Cells - pathology
Schwann Cells - virology
schwann-cells
Signal Transduction - immunology
Species Specificity
Staining
Strains (organisms)
Time Factors
TLR2 protein
tlr9
Toll-Like Receptor 2 - metabolism
Toll-Like Receptor 9 - metabolism
Toll-like receptors
Trigeminal ganglion
Trigeminal Ganglion - pathology
Trigeminal Ganglion - virology
Vibrissae - innervation
Vibrissae - virology
Virology/Animal Models of Infection
Virology/Effects of Virus Infection on Host Gene Expression
Virology/Host Antiviral Responses
Virology/Host Invasion and Cell Entry
virus
Virus Internalization
Viruses
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Summary:Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers area of DA rats, whereas PVG rats remained completely asymptomatic. In the present study we investigated the early immunokinetics in these strains to address the underlying molecular mechanisms for the observed difference. The virus distribution and the immunological responses were compared in the whiskers area, trigeminal ganglia and brain stem after 12 hours and the first four days following infection using immunohistochemistry and qRT-PCR. A conspicuous immunopathological finding was a strain-dependent difference in the spread of the HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi. In the whiskers area infected perineurial cells were abundant in the susceptible DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was confined only to the epineurium. In both strains activation of Iba1(+)/ED1(+) phagocytic cells followed the distribution pattern of HSV-1 staining, which was visible already at 12 hours after infection. Notably, in PVG rats higher mRNA expression of Toll-like receptors (Tlr) -2 and -9, together with increased staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other Tlr-pathway markers were expressed at higher levels in the susceptible DA rats. Our data demonstrate the novel observation that genetically encoded properties of the host nerve and perineurial cells, recruitment of phagocyting cells together with the low expression of Tlr2 and -9 in the periphery define the susceptibility to HSV-1 entry into the nervous system.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012350