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 membranebound 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.Dendritic cells (DCs) play a critical role in antigen presentation and are involved in the induction of primary T-cell responses (1,30,34). They are constitutively rich in major histocompatibility complex (MHC) class II molecules and can be induced to express costimulatory molecules such as B7.1 and B7.2, which are essential for the activation of naive T cells. DCs exist in two functional stages. Immature DCs develop from hematopoetic precursors and are scattered throughout the body in nonlymphoid organs, where they exert sentinel functions. DCs pick up and process antigens and subsequently migrate into lymphoid organs, a process which is paralleled by maturation. This maturation process is necessary to elicit an immune response and is induced in principle by inflammatory stimuli, such as cytokines, lipopolysaccharides, CpG-containing oligodeoxynucleotides, and cell-cell and cell-matrix contacts (1,24,32,42,45). In lymphoid organs mature DCs select and stimulate antigen-specific T cells.DCs are the critical antigen-presenting cells (APCs) involved in the immune response against microbes. A variety of pathogens such as human immunodeficiency virus type 1, measles virus, bacteria, or protozoa use DCs as host cells (7,23,37,38,40). However, internalization of Listeria monocytogenes into primary human DCs has not yet been shown.L. monocytogenes is a gram-positive human pathogenic bacterium, which is taken up via the orogastric route. After invading mucosal surfaces in the small i...