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Scrapie pathogenesis : the role of complement C1q in scrapie agent uptake by conventional dendritic cells
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Flores-Langarica, Adriana, Sebti, Yasmine, Mitchell, Daniel A., Sim, Robert B. and MacPherson, Gordon G. (2009) Scrapie pathogenesis : the role of complement C1q in scrapie agent uptake by conventional dendritic cells. Journal of Immunology, Vol.182 (No.3). pp. 1305-1313. ISSN 0022-1767.
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Official URL: http://www.jimmunol.org
Abstract
Mice lacking complement components show delayed development of prion disease following peripheral inoculation. The delay could relate to reduced scrapie prion protein (PrPSc) accumulation on follicular dendritic cells (DCs). However conventional DCs (cDCs) play a crucial role in the early pathogenesis of prion diseases and complement deficiency could result in decreased PrPSc uptake by cDCs in the periphery. To explore this possibility, we cultured murine splenic or gut-associated lymph node cDCs with scrapie-infected whole brain homogenate in the presence or absence of complement. Uptake decreased significantly if the serum in the cultures was heat-inactivated. Because heat inactivation primarily denatures C1q, we used serum from C1q(-/-) mice and showed that PrPSc uptake was markedly decreased. PrPSc internalization was saturable and temperature-dependent, suggesting receptor-mediated uptake. Furthermore, uptake characteristics differed from fluid-phase endocytosis. Immunofluorescence showed colocalization of C1q and PrPSc, suggesting interaction between these molecules. We evaluated the expression of several complement receptors on cDCs and confirmed that cDCs that take up PrPSc express one of the C1q receptors, calreticulin. Our results show that C1q participates in PrPSc uptake by cDCs, revealing a critical role for cDCs in initial prion capture, an event that takes place before the PrPSc accumulation within the follicular DC network. The Journal of Immunology, 2009, 182: 1305-1313.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QR Microbiology > QR180 Immunology | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Immunology | ||||
| Publisher: | American Association of Immunologists | ||||
| ISSN: | 0022-1767 | ||||
| Official Date: | 1 February 2009 | ||||
| Dates: |
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| Volume: | Vol.182 | ||||
| Number: | No.3 | ||||
| Number of Pages: | 9 | ||||
| Page Range: | pp. 1305-1313 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | European Community, Research Council U.K. | ||||
| Grant number: | FOOD-CT-2006-023144 |
Data sourced from Thomson Reuters' Web of Knowledge
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