title: CD46 in meningococcal disease.
abstract: The human-specific bacterial pathogen Neisseria meningitidis is a major cause of sepsis and/or meningitis. The pili of N. meningitidis interact with CD46, a human cell-surface protein involved in regulation of complement activation. Transgenic mice expressing human CD46 were susceptible to meningococcal disease, because bacteria crossed the blood-brain barrier in these mice. Development of disease was more efficient with piliated bacteria after intranasal, but not intraperitoneal, challenge of CD46 transgenic mice, suggesting that human CD46 facilitates pilus-dependent interactions at the epithelial mucosa. Hence, the human CD46 transgenic mice model is a potentially useful tool for studying pathogenesis and for vaccine development against meningococcal disease.
authors.affiliation: Microbiology and Tumor Biology Center, Nobels väg 16, Box 280, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.forename: Anne
authors.initials: A
authors.lastname: Rytkonen
authors.forename: Peter
authors.initials: P
authors.lastname: Bergman
authors.forename: Barbara
authors.initials: B
authors.lastname: Albiger
authors.forename: Helena
authors.initials: H
authors.lastname: Källström
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
authors.forename: Ann-Beth
authors.initials: AB
authors.lastname: Jonsson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D016470:Bacteremia; D001812:Blood-Brain Barrier; D002555:Cerebrospinal Fluid / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D010861:Fimbriae, Bacterial / Q000502:physiology; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D008585:Meningitis, Meningococcal / Q000382:microbiology*; D008589:Meningococcal Infections / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009305:Nasopharynx / Q000382:microbiology; D009345:Neisseria meningitidis / Q000472:pathogenicity* / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins