title: Identification of the insulin-like growth factor II receptor as a novel receptor for binding and invasion by Listeria monocytogenes.
abstract: The gram-positive bacterium Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor (CI)M6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.
authors.affiliation: Discipline of Immunology & Microbiology, Faculty of Health, The University of Newcastle, Royal Newcastle Hospital, Newcastle, New South Wales 2300, Australia.
authors.forename: Uta
authors.initials: U
authors.lastname: Gasanov
authors.forename: Craig
authors.initials: C
authors.lastname: Koina
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology*; D002460:Cell Line; D002846:Chromatography, Affinity; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism* / Q000502:physiology
chemical_list: D019151:Peptide Library; D010455:Peptides; D017527:Receptor, IGF Type 2