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Viral infection switches non-plasmacytoid dendritic cells into high interferon producers 总被引:1,自引:0,他引:1
Diebold SS Montoya M Unger H Alexopoulou L Roy P Haswell LE Al-Shamkhani A Flavell R Borrow P Reis e Sousa C 《Nature》2003,424(6946):324-328
Type I interferons (IFN-I) are important cytokines linking innate and adaptive immunity. Plasmacytoid dendritic cells make high levels of IFN-I in response to viral infection and are thought to be the major source of the cytokines in vivo. Here, we show that conventional non-plasmacytoid dendritic cells taken from mice infected with a dendritic-cell-tropic strain of lymphocytic choriomeningitis virus make similarly high levels of IFN-I on subsequent culture. Similarly, non-plasmacytoid dendritic cells secrete high levels of IFN-I in response to double-stranded RNA (dsRNA), a major viral signature, when the latter is introduced into the cytoplasm to mimic direct viral infection. This response is partially dependent on the cytosolic dsRNA-binding enzyme protein kinase R and does not require signalling through toll-like receptor (TLR) 3, a surface receptor for dsRNA. Furthermore, we show that sequestration of dsRNA by viral NS1 (refs 6, 7) explains the inability of conventional dendritic cells to produce IFN-I on infection with influenza. Our results suggest that multiple dendritic cell types, not just plasmacytoid cells, can act as specialized interferon-producing cells in certain viral infections, and reveal the existence of a TLR-independent pathway for dendritic cell activation that can be the target of viral interference. 相似文献
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Kamath RS Fraser AG Dong Y Poulin G Durbin R Gotta M Kanapin A Le Bot N Moreno S Sohrmann M Welchman DP Zipperlen P Ahringer J 《Nature》2003,421(6920):231-237
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Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6 总被引:12,自引:0,他引:12
Zhang Q Zhao B Li W Oiso N Novak EK Rusiniak ME Gautam R Chintala S O'Brien EP Zhang Y Roe BA Elliott RW Eicher EM Liang P Kratz C Legius E Spritz RA O'Sullivan TN Copeland NG Jenkins NA Swank RT 《Nature genetics》2003,33(2):145-153
Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles. 相似文献
138.
Huang E Ishida S Pittman J Dressman H Bild A Kloos M D'Amico M Pestell RG West M Nevins JR 《Nature genetics》2003,34(2):226-230
139.
A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis 总被引:14,自引:0,他引:14
Cooper MK Wassif CA Krakowiak PA Taipale J Gong R Kelley RI Porter FD Beachy PA 《Nature genetics》2003,33(4):508-513
Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis. Many of the developmental malformations in these syndromes occur in tissues and structures whose embryonic patterning depends on signaling by the Hedgehog (Hh) family of secreted proteins. Here we report that response to the Hh signal is compromised in mutant cells from mouse models of SLOS and lathosterolosis and in normal cells pharmacologically depleted of sterols. We show that decreasing levels of cellular sterols correlate with diminishing responsiveness to the Hh signal. This diminished response occurs at sterol levels sufficient for normal autoprocessing of Hh protein, which requires cholesterol as cofactor and covalent adduct. We further find that sterol depletion affects the activity of Smoothened (Smo), an essential component of the Hh signal transduction apparatus. 相似文献
140.