Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie

Evidence against dendritic cell involvement in neuroinvasion

Michael B.A. Oldstone, Richard Race, Diane Thomas, Hanna Lewicki, Dirk Homann, Sara Smelt, Andreas Holz, Pandelakis Koni, David Lo, Bruce Chesebro, Richard Flavell

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c+ lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-α) and LT-β P signaling components. We report here that by the oral route, LT-α -/- mice developed scrapie while LT-β -/- mice did not. Furthermore, LT-α -/- mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-β -/- mice. Transplantation of lymphoid tissues from LT-β -/- mice, which have cervical and mesenteric lymph nodes, into LT-α -/- mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c+ cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c+ cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-α -/- than in LT-β -/- mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.

Original languageEnglish (US)
Pages (from-to)4357-4363
Number of pages7
JournalJournal of Virology
Volume76
Issue number9
DOIs
StatePublished - Apr 25 2002

Fingerprint

lymphotoxin
Lymphotoxin-alpha
Scrapie
scrapie
dendritic cells
Dendritic Cells
Follicular Dendritic Cells
mice
Prion Diseases
prion diseases
Lymphoid Tissue
central nervous system
mouth
Central Nervous System
Infection
infection
cells
Lymphocytes
incidence
central nervous system diseases

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie : Evidence against dendritic cell involvement in neuroinvasion. / Oldstone, Michael B.A.; Race, Richard; Thomas, Diane; Lewicki, Hanna; Homann, Dirk; Smelt, Sara; Holz, Andreas; Koni, Pandelakis; Lo, David; Chesebro, Bruce; Flavell, Richard.

In: Journal of Virology, Vol. 76, No. 9, 25.04.2002, p. 4357-4363.

Research output: Contribution to journalArticle

Oldstone, MBA, Race, R, Thomas, D, Lewicki, H, Homann, D, Smelt, S, Holz, A, Koni, P, Lo, D, Chesebro, B & Flavell, R 2002, 'Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie: Evidence against dendritic cell involvement in neuroinvasion', Journal of Virology, vol. 76, no. 9, pp. 4357-4363. https://doi.org/10.1128/JVI.76.9.4357-4363.2002
Oldstone, Michael B.A. ; Race, Richard ; Thomas, Diane ; Lewicki, Hanna ; Homann, Dirk ; Smelt, Sara ; Holz, Andreas ; Koni, Pandelakis ; Lo, David ; Chesebro, Bruce ; Flavell, Richard. / Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie : Evidence against dendritic cell involvement in neuroinvasion. In: Journal of Virology. 2002 ; Vol. 76, No. 9. pp. 4357-4363.
@article{0083122a0db640259ddf7aa705de660f,
title = "Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie: Evidence against dendritic cell involvement in neuroinvasion",
abstract = "Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c+ lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-α) and LT-β P signaling components. We report here that by the oral route, LT-α -/- mice developed scrapie while LT-β -/- mice did not. Furthermore, LT-α -/- mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-β -/- mice. Transplantation of lymphoid tissues from LT-β -/- mice, which have cervical and mesenteric lymph nodes, into LT-α -/- mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c+ cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c+ cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-α -/- than in LT-β -/- mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.",
author = "Oldstone, {Michael B.A.} and Richard Race and Diane Thomas and Hanna Lewicki and Dirk Homann and Sara Smelt and Andreas Holz and Pandelakis Koni and David Lo and Bruce Chesebro and Richard Flavell",
year = "2002",
month = "4",
day = "25",
doi = "10.1128/JVI.76.9.4357-4363.2002",
language = "English (US)",
volume = "76",
pages = "4357--4363",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Lymphotoxin-α- and lymphotoxin-β-deficient mice differ in susceptibility to scrapie

T2 - Evidence against dendritic cell involvement in neuroinvasion

AU - Oldstone, Michael B.A.

AU - Race, Richard

AU - Thomas, Diane

AU - Lewicki, Hanna

AU - Homann, Dirk

AU - Smelt, Sara

AU - Holz, Andreas

AU - Koni, Pandelakis

AU - Lo, David

AU - Chesebro, Bruce

AU - Flavell, Richard

PY - 2002/4/25

Y1 - 2002/4/25

N2 - Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c+ lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-α) and LT-β P signaling components. We report here that by the oral route, LT-α -/- mice developed scrapie while LT-β -/- mice did not. Furthermore, LT-α -/- mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-β -/- mice. Transplantation of lymphoid tissues from LT-β -/- mice, which have cervical and mesenteric lymph nodes, into LT-α -/- mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c+ cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c+ cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-α -/- than in LT-β -/- mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.

AB - Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c+ lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-α) and LT-β P signaling components. We report here that by the oral route, LT-α -/- mice developed scrapie while LT-β -/- mice did not. Furthermore, LT-α -/- mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-β -/- mice. Transplantation of lymphoid tissues from LT-β -/- mice, which have cervical and mesenteric lymph nodes, into LT-α -/- mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c+ cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c+ cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-α -/- than in LT-β -/- mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection.

UR - http://www.scopus.com/inward/record.url?scp=0036230174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036230174&partnerID=8YFLogxK

U2 - 10.1128/JVI.76.9.4357-4363.2002

DO - 10.1128/JVI.76.9.4357-4363.2002

M3 - Article

VL - 76

SP - 4357

EP - 4363

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

ER -