Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor

Mol Microbiol. 2003 Aug;49(3):623-37. doi: 10.1046/j.1365-2958.2003.03591.x.

Abstract

Gonorrhea is characterized by a purulent urethral or cervical discharge consisting primarily of neutrophils associated with Neisseria gonorrhoeae. These interactions are facilitated by gonococcal colony opacity-associated (Opa) protein binding to host cellular CEACAM receptors. Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine-based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors. CEACAM3 was tyrosine phosphorylated by a Src family kinase-dependent process upon infection by gonococci expressing CEACAM-specific Opa proteins. This phosphorylation was necessary for efficient bacterial uptake; however, a less efficient uptake process became evident when kinase inhibitors or mutagenesis of the ITAM were used to prevent phosphorylation. Ligated CEACAM3 was recruited to a cytoskeleton-containing fraction, intense foci of polymerized actin were evident where bacteria attached to HeLa-CEACAM3, and disruption of polymerized actin by cytochalasin D blocked all bacterial uptake by these cells. These data support a model whereby CEACAM3 can mediate the Opa-dependent uptake of N. gonorrhoeae via either an efficient, ITAM phosphorylation-dependent process that resembles phagocytosis or a less efficient, tyrosine phosphorylation-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / ultrastructure
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antigens, Bacterial
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carcinoembryonic Antigen / chemistry
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • HeLa Cells / metabolism
  • HeLa Cells / microbiology
  • Humans
  • Molecular Sequence Data
  • Neisseria gonorrhoeae / genetics
  • Neisseria gonorrhoeae / metabolism*
  • Neutrophils / metabolism*
  • Neutrophils / microbiology
  • Neutrophils / ultrastructure
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • src-Family Kinases / metabolism*

Substances

  • Adhesins, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • CEACAM3 protein, human
  • Carcinoembryonic Antigen
  • Proteoglycans
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • opacity factor receptor, Neisseria gonorrhoeae
  • opacity proteins
  • src-Family Kinases