title: The cellular prion protein negatively regulates phagocytosis and cytokine expression in murine bone marrow-derived macrophages.
abstract: The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrP(C) in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrP(C) in phagocytosis and cytokine expression in bone marrow-derived macrophages infected with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA level. Knockout of PrP(C) promoted bacterial uptake; upregulated Rab5, Rab7, and Eea1 mRNA expression; and increased the recruitment of lysosomal-associated membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity. Remarkably, knockout of PrP(C) suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrP(C) as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity.
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Min
authors: M
authors: Wang
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Deming
authors: D
authors: Zhao
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Yang
authors: Y
authors: Yang
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Jin
authors: J
authors: Liu
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Jin
authors: J
authors: Wang
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Xiaomin
authors: X
authors: Yin
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Lifeng
authors: L
authors: Yang
authors: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Xiangmei
authors: X
authors: Zhou
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000254:growth & development; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics*; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D061251:Primary Cell Culture; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000276:immunology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D052119:Lysosomal-Associated Membrane Protein 2; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C485184:enhanced green fluorescent protein; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D049452:Green Fluorescent Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins