Interaction of Neisseria meningitidis with Human Dendritic Cells

doi:10.1128/IAI.69.11.6912-6922.2001

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Infection and Immunity, November 2001, p. 6912-6922, Vol. 69, No. 11
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

Annette Kolb-Mäurer,¹^,² Alexandra Unkmeir,¹ Ulrike Kämmerer,³ Claudia Hübner,¹ Thomas Leimbach,¹ Anne Stade,¹ Eckhart Kämpgen,⁴ Matthias Frosch,¹^,^* and Guido Dietrich¹^,^*

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 severityof disease directly correlates with the production of the proinflammatorycytokines tumor necrosis factor alpha (TNF- $alpha$ ), interleukin-1 (IL-1),IL-6, and IL-8. However, the source of these cytokines has notbeen clearly defined yet. Since bacterial infection involves theactivation of dendritic cells (DCs), we analyzed the interactionof N. meningitidis with monocyte-derived DCs. Using N. meningitidisserogroup B wild-type and unencapsulated bacteria, we found thatcapsule expression significantly impaired neisserial adherenceto DCs. In addition, phagocytic killing of the bacteria in thephagosome is reduced by at least 10- to 100-fold. However, allstrains induced strong secretion of proinflammatory cytokinesTNF- $alpha$ , IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection[p.i.]), with significantly increased cytokine levels being measurableby as early as 6 h p.i. Levels of IL-1 $beta$ , in contrast, were increasedonly 200- to 400-fold at 20 h p.i. with barely measurable inductionat 6 h p.i. Moreover, comparable amounts of cytokines were inducedby bacterium-free supernatants of Neisseria cultures containingneisserial lipooligosaccharide as the main factor. Our data suggestthat activated DCs may be a significant source of high levelsof proinflammatory cytokines in neisserial infection and therebymay contribute to the pathology of meningococcaldisease.

^* 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 MatthiasFrosch (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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