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Infection and Immunity, November 2001, p. 6912-6922, Vol. 69, No. 11
Institut für Hygiene und Mikrobiologie,
Universität Würzburg,1
Universitätsklinik für
Frauenheilkunde,3 and
Dermatologische Universitätsklinik
Würzburg,4 97080 Würzburg, and
Lehrstuhl für Mikrobiologie,
Theodor-Boveri-Institut für Biowissenschaften der
Universität Würzburg, 97074 Würzburg,2 Germany
Received 20 April 2001/Returned for modification 26 June
2001/Accepted 10 August 2001
Infection with Neisseria meningitidis serogroup B is
responsible for fatal septicemia and meningococcal meningitis. The
severity of disease directly correlates with the production of the
proinflammatory cytokines tumor necrosis factor alpha (TNF-
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.11.6912-6922.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Interaction of Neisseria
meningitidis with Human Dendritic Cells
),
interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these
cytokines has not been clearly defined yet. Since bacterial
infection involves the activation of dendritic cells (DCs), we analyzed
the interaction of N. meningitidis with monocyte-derived
DCs. Using N. meningitidis serogroup B
wild-type and unencapsulated bacteria, we found that capsule expression
significantly impaired neisserial adherence to DCs. In addition,
phagocytic killing of the bacteria in the phagosome is reduced by at
least 10- to 100-fold. However, all strains induced strong secretion of
proinflammatory cytokines TNF-
, IL-6, and IL-8 by DCs (at least
1,000-fold at 20 h postinfection [p.i.]), with significantly
increased cytokine levels being measurable by as early as 6 h p.i.
Levels of IL-1
, in contrast, were increased only 200- to 400-fold at
20 h p.i. with barely measurable induction at 6 h p.i.
Moreover, comparable amounts of cytokines were induced by
bacterium-free supernatants of Neisseria cultures
containing neisserial lipooligosaccharide as the main factor. Our data
suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may
contribute to the pathology of meningococcal disease.
*
Corresponding author. Present address for Guido
Dietrich: Bacterial Vaccine Research, Berna Biotech AG, Rehhagstrasse
79, 3018 Berne, Switzerland. Phone: 41-31-980-6372. Fax:
41-31-980-6785. E-mail: guido.dietrich{at}bernabiotech.com.
Mailing address for Matthias Frosch (for reprint requests): Institut
für Hygiene und Mikrobiologie, Universität Würzburg,
Josef-Schneider Strasse 2, 97080 Würzburg, Germany. Phone:
49-931-201-5161. Fax: 49-931-201-3445. E-mail: mfrosch{at}hygiene.uni-wuerzburg.de.
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