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Science 18 July 2003:
Vol. 301. no. 5631, pp. 373 - 375
DOI: 10.1126/science.1086476
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Reports

CD46 in Meningococcal Disease

Linda Johansson,1 Anne Rytkönen,1 Peter Bergman,2 Barbara Albiger,5 Helena Källström,3 Tomas Hökfelt,4 Birgitta Agerberth,2 Roberto Cattaneo,6 Ann-Beth Jonsson1*

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.

1 Microbiology and Tumor Biology Center, Nobels väg 16, Box 280, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 2 Department of Medical Biochemistry and Biophysics, 3 Department of Cell and Molecular Biology, 4 Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 5 Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. 6 Molecular Medicine Program, Mayo Clinic, Guggenheim 1838, 200 First Street SW, Rochester, MN 55905, USA.

* To whom correspondence should be addressed. E-mail: Ann-Beth.Jonsson{at}mtc.ki.se

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