Listeria monocytogenes-infected human dendritic cells: uptake and host cell response.
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.
Kolb-Mäurer
A
A
Lehrstuhl für Mikrobiologie, Theodor-Boveri-Institut für Biowissenschaften der Universität Würzburg, 97074 Würzburg, Germany.ankolb@biozentrum.uniwuerzburg.de
Gentschev
I
I
Fries
H W
HW
Fiedler
F
F
Bröcker
E B
EB
Kämpgen
E
E
Goebel
W
W
D015703:Antigens, CD / Q000302:isolation & purification; D051940:B7-2 Antigen; D001773:Blood Cells; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D006459:Hemolysin Factors / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000302:isolation & purification; D006801:Humans; D007136:Immunoglobulins / Q000302:isolation & purification; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008562:Membrane Glycoproteins / Q000302:isolation & purification; D009154:Mutation; D009336:Necrosis; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000382:microbiology; D015375:Receptors, Interleukin-2 / Q000302:isolation & purification; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D000097802:CD83 Antigen; C497964:CD86 protein, human