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Infection and Immunity, June 2000, p. 3680-3688, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Listeria monocytogenes-Infected Human Dendritic Cells: Uptake and Host Cell Response

Annette Kolb-Mäurer,1,* Ivaylo Gentschev,1 Hans-Werner Fries,2 Franz Fiedler,3 Eva-Bettina Bröcker,2 Eckhart Kämpgen,2 and Werner Goebel1

Lehrstuhl für Mikrobiologie, Theodor-Boveri-Institut für Biowissenschaften der Universität Würzburg, 97074 Würzburg,1 Dermatologische Universitätsklinik Würzburg, 97080 Würzburg,2 and Lehrstuhl für Mikrobiologie, Universität München, 80638 Munich,3 Germany

Received 22 December 1999/Accepted 29 February 2000

Dendritic cells (DCs) are potent antigen-presenting cells and play a crucial role in initiation and modulation of specific immune responses. Various pathogens are able to persist inside DCs. However, internalization of the gram-positive bacterium Listeria monocytogenes into human DCs has not yet been shown. In the present study, we demonstrate that human monocyte-derived immature DCs can efficiently phagocytose L. monocytogenes. This uptake is independent of listerial adhesion factors internalin A and internalin B but requires cytoskeletal motion and factors present in human plasma. A major portion of internalized bacteria is found in membrane-bound phagosomes and is rarely free in the cytosol, as shown by transmission electron microscopy and by using an L. monocytogenes strain expressing green fluorescent protein when in the host cell cytosol. The infection caused maturation of the immature DCs into mature DCs displaying high levels of CD83, CD25, major histocompatibility complex class II, and the CD86 costimulator molecule. This effect appeared to be largely mediated by listerial lipoteichoic acid. Although L. monocytogenes infection is known to induce death in other cell types, infection of human DCs was found to induce necrotic but not apoptotic death in fewer than 20% of DCs. Therefore, the ability of DCs to act as effective antigen-presenting cells for listerial immunity is probably enhanced by their resistance to cell death, as well as their ability to rapidly differentiate into mature, immunostimulatory DCs upon encountering bacteria.

* Corresponding author. Mailing address: Lehrstuhl für Mikrobiologie, Theodor-Boveri-Institut für Biowissenschaften der Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. Phone: (49) 931-8884401. Fax: (49) 931-8884402. E-mail: ankolb{at}biozentrum.uni-wuerzburg.de.

Infection and Immunity, June 2000, p. 3680-3688, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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