Dendritic cells (DC) play a crucial role in the immune system as they are the professional antigen-presenting cells (APCs) most efficient in the activation of resting T lymphocytes and thus initiate primary immune responses. This activity is believed to be crucially controlled by micro environmental signals. DC have a privileged distribution in tissues interfacing the external environment thus acting as efficient sentinels for recognition of invading microorganisms. Consistent with this hypothesis, we have shown that DC can internalize bacteria into phagosomes and that both gram-positive and gram-negative bacteria function as DC activators. The ability of DC to phagocytose particulates or bacteria is more pronounced in immature, less-differentiated cells than in mature DC, this capacity being downregulated upon activation. Activation of DC by bacteria can be shown phenotypically. Incubation of DCs with different bacteria including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus gordonii, Staphylococcus aureus, Lactococcus lactis, Lactobacillus acidophilus, Mycobacterium smegmatis, Salmonella Ty21a, Escherichia coli, Mycobacterium etc. resulted in modification of surface activation markers. Consistent with acquisition of costimulating activity is the upregulation of both B7.2 (CD86) and CD40. The binding of B7.2 with its ligand on T cells (CD28 or CTLA-4) results in a costimulatory signal for cytokine production and T cell proliferation. Functional DC activation was followed using well characterized T cell hybridomas specific for peptides of ovalbumin (OVA) and a recombinant strain of Streptococcus gordonii engineered to express OVA.