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.
Highlights
Phagocytosis of pathogens initiates the innate immune response [1,2]
Knockout of prion protein gene (PRNP) promoted phagocytosis we examined the expression of PrPC in BMDMs from
To determine the role of PrPC in phagocytic activity, BMDMs from PRNP2/2 and wild-type mice were infected with Enhanced green fluorescent protein (EGFP)-E. coli for 30 and 60 min, and the phagocytic index (PI) was assessed as a measure of the phagocytic capacity
Summary
Phagocytosis of pathogens initiates the innate immune response [1,2]. Macrophages rely heavily on phagocytosis and subsequent degradation of microbes to help clear the invading pathogens [3]. Nascent phagosomes lack the ability to kill pathogens and degrade ingested targets; these properties are acquired during the process of phagosome maturation [4]. Targets are delivered from phagosomes to lysosomes for degradation [5]. The low-molecular-weight GTPases Rab and Rab, which govern the fusion of phagosomes with early and late endosomes, are associated with phagosome maturation [2,6]. Late phagosomes acquire markers such as lysosomal-associated membrane protein (LAMP)-1 and LAMP-2, which are required for acquisition of Rab and microbicidal properties [8]. These markers are important for phagosome fusion and maturation
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