Tumor necrosis factor alpha-deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie

被引:109
作者
Mabbott, NA
Williams, A
Farquhar, CF
Pasparakis, M
Kollias, G
Bruce, ME
机构
[1] Inst Anim Hlth, Neuropathogenesis Unit, Edinburgh EH9 3JF, Midlothian, Scotland
[2] Hellen Pasteur Inst, Athens 11521, Greece
关键词
D O I
10.1128/JVI.74.7.3338-3344.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS), Cells within the germinal centers (GCs) of the spleen and lymph nodes are important sites of extraneural replication from which infection is likely to spread to the CNS along peripheral nerves. Here, using immunodeficient mice, we investigate the identity of the cells in the spleen that are important for disease propagation. Despite possessing functional T and B lymphocytes, tumor necrosis factor alpha-deficient (TNF-alpha(-/-)) mice lack GCs and follicular dendritic cell (FDC) networks in lymphoid tissues. In contrast, lymphoid tissues of interleukin-6-deficient (IL-6(-/-)) mice possess FDC networks but have impaired GCs. When the CNSs of TNF-alpha(-/-), IL-6(-/-), and wild-type mice were directly challenged with the ME7 scrapie strain, 100% of the mice were susceptible, developing disease after closely similar incubation periods, However, when challenged peripherally (intraperitoneally), most TNF-alpha(-/-) mice failed to develop scrapie up to 503 days postinjection. All wild-type and IL-6(-/-) mice succumbed to disease approximately 300 days after the peripheral challenge, High levels of scrapie infection and the disease-specific isomer of the prion protein, PrPSc, were detectable in spleens from challenged wild-type and IL-6(-/-) mice but not from TNF-alpha(-/-) mice. Histopathological analysis of spleen tissue demonstrated heavy PrP accumulations in direct association with FDCs in challenged wild-type and IL-6(-/-) mice, No PrPSc accumulation was detected in spleens from TNF-alpha(-/-) mice. We conclude that, for the ME7 scrapie strain, mature FDCs are critical for replication in lymphoid tissues and that in their absence, neuroinvasion following peripheral challenge is impaired.
引用
收藏
页码:3338 / 3344
页数:7
相关论文
共 48 条
[31]   T-lymphocyte activation and the cellular form of the prion protein [J].
Mabbott, NA ;
Brown, KL ;
Manson, J ;
Bruce, ME .
IMMUNOLOGY, 1997, 92 (02) :161-165
[32]   Turning off follicular dendritic cells [J].
Mackay, F ;
Browning, JL .
NATURE, 1998, 395 (6697) :26-27
[33]   Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers [J].
Matsumoto, M ;
Mariathasan, S ;
Nahm, MH ;
Baranyay, F ;
Peschon, JJ ;
Chaplin, DD .
SCIENCE, 1996, 271 (5253) :1289-1291
[34]   Pathological PrP is abundant in sympathetic and sensory ganglia of hamsters fed with scrapie [J].
McBride, PA ;
Beekes, M .
NEUROSCIENCE LETTERS, 1999, 265 (02) :135-138
[35]   PRP PROTEIN IS ASSOCIATED WITH FOLLICULAR DENDRITIC CELLS OF SPLEENS AND LYMPH-NODES IN UNINFECTED AND SCRAPIE-INFECTED MICE [J].
MCBRIDE, PA ;
EIKELENBOOM, P ;
KRAAL, G ;
FRASER, H ;
BRUCE, ME .
JOURNAL OF PATHOLOGY, 1992, 168 (04) :413-418
[36]   ACTIVATION OF MICROGLIAL CELLS BY BETA-AMYLOID PROTEIN AND INTERFERON-GAMMA [J].
MEDA, L ;
CASSATELLA, MA ;
SZENDREI, GI ;
OTVOS, L ;
BARON, P ;
VILLALBA, M ;
FERRARI, D ;
ROSSI, F .
NATURE, 1995, 374 (6523) :647-650
[37]   SEPARATION AND PROPERTIES OF CELLULAR AND SCRAPIE PRION PROTEINS [J].
MEYER, RK ;
MCKINLEY, MP ;
BOWMAN, KA ;
BRAUNFELD, MB ;
BARRY, RA ;
PRUSINER, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (08) :2310-2314
[38]   Immune and inflammatory responses in TNF alpha-deficient mice: A critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response [J].
Pasparakis, M ;
Alexopoulou, L ;
Episkopou, V ;
Kollias, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (04) :1397-1411
[39]   TNF-alpha transgenic and knockout models of CNS inflammation and degeneration [J].
Probert, L ;
Akassoglou, K ;
Kassiotis, G ;
Pasparakis, M ;
Alexopoulou, L ;
Kollias, G .
JOURNAL OF NEUROIMMUNOLOGY, 1997, 72 (02) :137-141
[40]   FURTHER PURIFICATION AND CHARACTERIZATION OF SCRAPIE PRIONS [J].
PRUSINER, SB ;
BOLTON, DC ;
GROTH, DF ;
BOWMAN, KA ;
COCHRAN, SP ;
MCKINLEY, MP .
BIOCHEMISTRY, 1982, 21 (26) :6942-6950