title: EspJ of enteropathogenic and enterohaemorrhagic Escherichia coli inhibits opsono-phagocytosis.
abstract: A key strategy in microbial pathogenesis is the subversion of the first line of cellular immune defences presented by professional phagocytes. Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC respectively) remain extracellular while colonizing the gut mucosa by attaching and effacing mechanism. EPEC use the type three secretion system effector protein EspF to prevent their own uptake into macrophages. EPEC can also block in trans the internalization of IgG-opsonized particles. In this study, we show that EspJ is the type three secretion system effector protein responsible for trans-inhibition of macrophage opsono-phagocytosis by both EPEC and EHEC. While EspF plays no role in trans-inhibition of opsono-phagocytosis, espJ mutants of EPEC or EHEC are unable to block uptake of opsonized sheep red blood cells (RBC), a phenotype that is rescued upon complementation with the espJ gene. Importantly, ectopic expression of EspJ(EHEC) in phagocytes is sufficient to inhibit internalization of both IgG- and C3bi-opsonized RBC. These results suggest that EspJ targets a basic mechanism common to these two unrelated phagocytic receptors. Moreover, EspF and EspJ target independent aspects of the phagocytic function of mammalian macrophages in vitro.
authors.affiliation: Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Marchès
authors.forename: Valentina
authors.initials: V
authors.lastname: Covarelli
authors.forename: Sivan
authors.initials: S
authors.lastname: Dahan
authors.forename: Céline
authors.initials: C
authors.lastname: Cougoule
authors.forename: Pallavi
authors.initials: P
authors.lastname: Bhatta
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Caron
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D054324:Enterohemorrhagic Escherichia coli / Q000378:metabolism*; D019453:Escherichia coli O157 / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D016177:Macrophage-1 Antigen / Q000276:immunology; D008264:Macrophages / Q000382:microbiology*; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; C497366:EspJ protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins