title: The role of beta2 integrins and lipopolysaccharide-binding protein in the phagocytosis of dead Neisseria meningitidis.
abstract: Phagocytosis of microbial pathogens is essential for the host immune response to infection. Our previous work has shown that lipooligosaccharide (LOS) expression on the surface of Neisseria meningitidis (Nm) is essential for phagocytosis, but the receptor involved remained unclear. In this study, we show that human CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are phagocytic receptors for Nm as illustrated by the capacity of CR3- and CR4-transfected Chinese hamster ovary (CHO) cells to facilitate Nm uptake. A CR3-signalling mutant failed to internalize Nm, showing that the ability of CR3 to signal is essential for phagocytosis. Internalization of Nm by CR3-transfected CHO cells could be inhibited by the presence of CR3-specific antibodies. Furthermore, dendritic cells from leukocyte adhesion deficiency-1 patients, who have diminished expression of beta2 integrins, showed markedly reduced phagocytosis of Nm. The CR3-mediated phagocytosis required the presence of lipopolysaccharide-binding protein (LBP). Furthermore, the expression of LOS by Nm was essential for LBP binding and phagocytosis via CR3. These results reveal a critical role of CR3 and LBP in the phagocytosis of Nm and provide important insights into the initial interaction meningococci have with the immune system.
authors.affiliation: Immunobiology and Infectious Diseases and Microbiology Units, Institute of Child Health, University College London, London, UK. h.jones@ich.ucl.ac.uk
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Jones
authors.forename: Jessica
authors.initials: J
authors.lastname: Strid
authors.forename: Mohamed
authors.initials: M
authors.lastname: Osman
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: Garth
authors.initials: G
authors.lastname: Dixon
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
authors.forename: Robin E
authors.initials: RE
authors.lastname: Callard
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology*; D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000276:immunology; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D010587:Phagocytosis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D039481:CD11b Antigen; D018821:CD18 Antigens; D002352:Carrier Proteins; D016167:Integrin alphaXbeta2; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein; C023023:lipid-linked oligosaccharides