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.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Virus Internalization*; Central Nervous System/*virology ; Encephalitis, Viral/*metabolism ; Herpesvirus 1, Human/*physiology ; Peripheral Nerves/*pathology ; Toll-Like Receptor 2/*metabolism ; Toll-Like Receptor 9/*metabolism; Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/virology ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Dendritic Cells/immunology ; Dendritic Cells/virology ; Encephalitis, Viral/immunology ; Encephalitis, Viral/virology ; Gene Expression Regulation/immunology ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class II/metabolism ; Humans ; Immunity, Innate ; Inflammation Mediators/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/virology ; Kinetics ; Macrophages/immunology ; Macrophages/virology ; Male ; Peripheral Nerves/metabolism ; Peripheral Nerves/virology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; Schwann Cells/pathology ; Schwann Cells/virology ; Signal Transduction/immunology ; Species Specificity ; Time Factors ; Trigeminal Ganglion/pathology ; Trigeminal Ganglion/virology ; Vibrissae/innervation ; Vibrissae/virology

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.

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0 (Histocompatibility Antigens Class I)
0 (Histocompatibility Antigens Class II)
0 (Inflammation Mediators)
0 (RNA, Messenger)
0 (Toll-Like Receptor 2)
0 (Toll-Like Receptor 9)

Date Created: 20100901 Date Completed: 20101104 Latest Revision: 20240313

20250114

PMC2929186

10.1371/journal.pone.0012350

20806060