The Cellular Prion Protein Negatively Regulates Phagocytosis and Cytokine Expression in Murine Bone Marrow-Derived Macrophages |
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| Authors: | Min Wang Deming Zhao Yang Yang Jin Liu Jin Wang Xiaomin Yin Lifeng Yang Xiangmei Zhou |
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| Affiliation: | 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.; University of Melbourne, Australia, |
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| Abstract: | The cellular prion protein (PrPC) is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrPC in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrPC 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 PrPC 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 PrPC suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrPC as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity. |
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