DOI: 10.1038/sj.embor.embor731. Prion pathogenesis in the absence of Toll‐like receptor signalling

Prion pathogenesis in the absence of Toll‐like receptor signalling

10.1038/sj.embor.embor731

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

Abstract

To reach the brain from peripheral sites, prions must colonize various cell types within the lymphoreticular compartment. However, no prion entry receptors are yet known. Toll‐like receptors (TLRs) are pattern‐recognition receptors that bind a multitude of pathogens and are therefore candidates as effectors of prion entry. Moreover, injection of unmethylated CpG oligodinucleotides, which stimulate TLR9, has been reported to delay peripherally initiated scrapie. We therefore studied prion infection in MyD88−/− mice, which are defective in TLR signalling. Despite subtle defects in splenic microarchitecture, MyD88−/− mice challenged intraperitoneally or intracerebrally were fully susceptible to disease and died of scrapie after similar incubation times to those of wild‐type mice. Splenic infectivity titres rose to similar levels with the same kinetics, and brains showed similar histopathological changes. TLR signalling therefore does not have any major role in prion pathogenesis, and the protective effect of TLR stimulation is unlikely to result from direct interactions with prions.

Bibliography

Prinz, M., Heikenwalder, M., Schwarz, P., Takeda, K., Akira, S., & Aguzzi, A. (2003). Prion pathogenesis in the absence of Tollâlike receptor signalling. EMBO Reports, 4(2), 195â199. Portico.

Authors 6

Marco Prinz (first)
Mathias Heikenwalder (additional)
Petra Schwarz (additional)
Kiyoshi Takeda (additional)
Shizuo Akira (additional)
Adriano Aguzzi (additional)

References 29 Referenced 70

Dates

Type	When
Created	22 years, 6 months ago (Feb. 28, 2003, 2:58 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:55 p.m.)
Indexed	1 year ago (Aug. 5, 2024, 10:41 p.m.)
Issued	22 years, 7 months ago (Feb. 1, 2003)
Published	22 years, 7 months ago (Feb. 1, 2003)
Published Online	22 years, 7 months ago (Feb. 1, 2003)
Published Print	22 years, 7 months ago (Feb. 1, 2003)

Funders 0

None

BibTeX

@article{Prinz_2003, title={Prion pathogenesis in the absence of Toll‐like receptor signalling}, volume={4}, ISSN={1469-3178}, url={http://dx.doi.org/10.1038/sj.embor.embor731}, DOI={10.1038/sj.embor.embor731}, number={2}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Prinz, Marco and Heikenwalder, Mathias and Schwarz, Petra and Takeda, Kiyoshi and Akira, Shizuo and Aguzzi, Adriano}, year={2003}, month=feb, pages={195–199} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        8,
        6
      ]
    ],
    "date-time": "2024-08-06T02:41:53Z",
    "timestamp": 1722912113572
  },
  "reference-count": 29,
  "publisher": "Springer Science and Business Media LLC",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2003,
            2,
            1
          ]
        ],
        "date-time": "2003-02-01T00:00:00Z",
        "timestamp": 1044057600000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [
      "www.embopress.org"
    ],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2003,
        2
      ]
    ]
  },
  "abstract": "<jats:p>To reach the brain from peripheral sites, prions must colonize various cell types within the lymphoreticular compartment. However, no prion entry receptors are yet known. Toll\u2010like receptors (TLRs) are pattern\u2010recognition receptors that bind a multitude of pathogens and are therefore candidates as effectors of prion entry. Moreover, injection of unmethylated CpG oligodinucleotides, which stimulate TLR9, has been reported to delay peripherally initiated scrapie. We therefore studied prion infection in <jats:italic>MyD88<jats:sup>\u2212/\u2212</jats:sup></jats:italic> mice, which are defective in TLR signalling. Despite subtle defects in splenic microarchitecture, <jats:italic>MyD88<jats:sup>\u2212/\u2212</jats:sup></jats:italic> mice challenged intraperitoneally or intracerebrally were fully susceptible to disease and died of scrapie after similar incubation times to those of wild\u2010type mice. Splenic infectivity titres rose to similar levels with the same kinetics, and brains showed similar histopathological changes. TLR signalling therefore does not have any major role in prion pathogenesis, and the protective effect of TLR stimulation is unlikely to result from direct interactions with prions.</jats:p>",
  "DOI": "10.1038/sj.embor.embor731",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        2,
        28
      ]
    ],
    "date-time": "2003-02-28T19:58:50Z",
    "timestamp": 1046462330000
  },
  "page": "195-199",
  "update-policy": "http://dx.doi.org/10.1002/crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 70,
  "title": "Prion pathogenesis in the absence of Toll\u2010like receptor signalling",
  "prefix": "10.1038",
  "volume": "4",
  "author": [
    {
      "given": "Marco",
      "family": "Prinz",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Institute of Neuropathology, University Hospital of Z\u00fcrich  Schmelzbergstrasse 12 CH\u20108091 Zrich Switzerland"
        }
      ]
    },
    {
      "given": "Mathias",
      "family": "Heikenwalder",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Neuropathology, University Hospital of Z\u00fcrich  Schmelzbergstrasse 12 CH\u20108091 Zrich Switzerland"
        }
      ]
    },
    {
      "given": "Petra",
      "family": "Schwarz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Neuropathology, University Hospital of Z\u00fcrich  Schmelzbergstrasse 12 CH\u20108091 Zrich Switzerland"
        }
      ]
    },
    {
      "given": "Kiyoshi",
      "family": "Takeda",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Host Defense, Research Institute for Microbial Diseases, Osaka University  3\u20101 Yamada\u2010oka Osaka 565\u20100871 Japan"
        }
      ]
    },
    {
      "given": "Shizuo",
      "family": "Akira",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Host Defense, Research Institute for Microbial Diseases, Osaka University  3\u20101 Yamada\u2010oka Osaka 565\u20100871 Japan"
        }
      ]
    },
    {
      "given": "Adriano",
      "family": "Aguzzi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Neuropathology, University Hospital of Z\u00fcrich  Schmelzbergstrasse 12 CH\u20108091 Zrich Switzerland"
        }
      ]
    }
  ],
  "member": "297",
  "published-online": {
    "date-parts": [
      [
        2003,
        2
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1074-7613(00)80596-8"
    },
    {
      "key": "e_1_2_6_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35052063"
    },
    {
      "key": "e_1_2_6_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35094583"
    },
    {
      "key": "e_1_2_6_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1996.tb00467.x"
    },
    {
      "key": "e_1_2_6_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35092578"
    },
    {
      "key": "e_1_2_6_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.192.4.595"
    },
    {
      "key": "e_1_2_6_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35074106"
    },
    {
      "key": "e_1_2_6_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35047123"
    },
    {
      "key": "e_1_2_6_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ni758"
    },
    {
      "key": "e_1_2_6_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1034/j.1600-0463.2002.100106.x"
    },
    {
      "key": "e_1_2_6_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.75.15.7097-7106.2001"
    },
    {
      "key": "e_1_2_6_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.164.2.768"
    },
    {
      "key": "e_1_2_6_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1074-7613(00)80086-2"
    },
    {
      "key": "e_1_2_6_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/37789"
    },
    {
      "key": "e_1_2_6_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/86567"
    },
    {
      "key": "e_1_2_6_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.148.8.2331"
    },
    {
      "key": "e_1_2_6_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0167-5699(00)01737-0"
    },
    {
      "key": "e_1_2_6_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80172-5"
    },
    {
      "key": "e_1_2_6_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/86562"
    },
    {
      "key": "e_1_2_6_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(00)80136-7"
    },
    {
      "key": "e_1_2_6_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.288.5469.1257"
    },
    {
      "key": "e_1_2_6_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.278.5343.1612"
    },
    {
      "key": "e_1_2_6_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.022626399"
    },
    {
      "key": "e_1_2_6_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/ana.410110406"
    },
    {
      "key": "e_1_2_6_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0140-6736(02)09513-2"
    },
    {
      "key": "e_1_2_6_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.4049/jimmunol.164.2.554"
    },
    {
      "key": "e_1_2_6_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/jnen/60.2.173"
    },
    {
      "key": "e_1_2_6_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.052703499"
    },
    {
      "key": "e_1_2_6_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0006-8993(94)90480-4"
    }
  ],
  "container-title": "EMBO reports",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1038/sj.embor.embor731",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1038/sj.embor.embor731",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://www.embopress.org/doi/pdf/10.1038/sj.embor.embor731",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        12,
        18
      ]
    ],
    "date-time": "2023-12-18T20:55:51Z",
    "timestamp": 1702932951000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.embopress.org/doi/10.1038/sj.embor.embor731"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2003,
        2
      ]
    ]
  },
  "references-count": 29,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2003,
          2
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1038/sj.embor.embor731"
  ],
  "URL": "http://dx.doi.org/10.1038/sj.embor.embor731",
  "relation": {},
  "ISSN": [
    "1469-221X",
    "1469-3178"
  ],
  "subject": [],
  "container-title-short": "EMBO Reports",
  "published": {
    "date-parts": [
      [
        2003,
        2
      ]
    ]
  },
  "assertion": [
    {
      "value": "2002-09-18",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2002-11-21",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2003-02-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}