Dendritic cells (DC) represent a class of professional antigen-presenting cells whose primary function is to alert the immune system, not to clear invading microorganisms. The objective of our study was to compare the abilities of polymorphonuclear neutrophilic leukocytes (PMN), monocytes, monocyte-derived macrophages (MDM), monocyte-derived immature DC (imDC), and mature DC (maDC) to ingest and destroy Staphylococcus aureus and Escherichia coli. Acridine orange staining and fluorescence microscopy demonstrated that MDM, followed by monocytes, imDC, and PMN, internalized bacteria well but that maDC exhibited less pronounced phagocytic activity. PMN, monocytes, and MDM exhibited a much higher capacity to kill ingested bacteria than both imDC and maDC. In summary, these data are in agreement with the generally accepted idea that different types of leukocytes fulfill specialized tasks in antigen presentation and killing of pathogens.

Dendritic cells (DC) represent a unique set of APCs that initiate immune responses through priming of naive T cells. Maturation of DC is a crucial step during Ag presentation and can be induced by triggering a broad spectrum of DC surface receptors. Although human DC express several receptors for the Fc portion of IgG which were described to play an important role in Ag internalization, little is known about the effects of IgG or immune complexes on DC maturation. In this study, we show that cross-linking of FcγR-type II (CD32) with immobilized IgG (imIgG) can induce maturation of human monocyte-derived DC via the NF-κB signaling pathway. IgG-mediated maturation was accompanied by a moderate increase of IL-10 secretion, whereas no IL-12 production was observed. Involvement of CD32 was further supported by experiments with the anti-CD32 mAb, which blocked IgG-triggered DC maturation and cytokine secretion significantly. Furthermore, DC cultivated in the presence of imIgG induced allogeneic T cell proliferation. Because this imIgG-induced maturation was considerably impaired in monocyte-derived DC from systemic lupus erythematosus patients, we suggest that DC, which matured in the presence of immune complexes, may contribute to prevention of pathological immune responses.

This review focuses on interactions of HIV with the first-line defence of native immunity, the complement system. In all body compartments tested so far, HIV meets complement. Activation of the complement system results in deposition of C3 fragments on the viral surface, but in contrast to other pathogens, most of HIV is not or is only poorly lysed by membrane attack complexes. To survive complement-mediated lysis, HIV has not only developed resistance mechanisms, but uses opsonisation with complement fragments for its own advantage. Opsonised virions interact with complement receptor-expressing cells, which are either subsequently infected with high efficiency or retain viral particles on their surface, which promotes transmission of virus to other permissive cells. Our knowledge of these mechanisms has increased enormously over the past few years. A complete understanding of these complex interactions of HIV with the complement system opens new perspectives for development of alternative therapeutic strategies.

After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.

In the present study we show that pentacyclic but not tetracyclic oxindole alkaloids from Uncoria tomentosa (Willd.) DC. (Rubiaceae) induced EA.hy926 endothelial cells to release some yet to be determined factor(s) into the supernatant; this factor was shown to significantly enhance proliferation of normal human resting or weakly activated B and T lymphocytes. In contrast, proliferation of normal human lymphoblasts and of both the human lymphoblastoid B cell line Raji and the human lymphoblastoid T cell line Jurkat was inhibited significantly while cell viability was not affected. Tetracyclic oxindole alkaloids dose-dependently reduce the activity of pentacyclic oxindole alkaloids on human endothelial cells.

Mononuclear phagocytes, which include circulating blood monocytes and differentiated tissue macrophages, are believed to play a central role in the sexual transmission of HIV infection. The ability of HIV to productively infect these cells may be influenced by action of exogenous or host-derived substances at the site of viral entry. Given the potent capacities of inflammatory mediators to stimulate anaphylatoxic and immunomodulatory functions in mucosa, the effects of complement-derived anaphylatoxins on the susceptibility of monocytes and monocyte-derived macrophages (MDM) to HIV-1 infection were examined. In our in vitro system, the susceptibility to infection was up to 40 times increased in MDM that had been exposed to C5a or C5adesArg, but not to C3a or C3adesArg, for 2 days before adding of virus. By contrast, the treatment with complement anaphylatoxins did not affect HIV replication in fresh monocytes. Stimulatory effect of C5a and its desArg derivative on HIV infection correlated with the increase of TNF-α and IL-6 secretion from MDM. All these functional effects of C5a and C5adesArg were reversible by treatment of cells with the mAb that functionally blocks C5aR. Taken together, these results indicate that C5a and C5adesArg may increase the susceptibility of MDM to HIV infection through stimulation of TNF-α and IL-6 secretion from these cells.

These findings indicate that in the GC infectious virus is trapped on CR2-expressing FDC (or B cells). Reduction of this pool of HIV could be a therapeutic goal.

SUMMARYIL-15 is a novel cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2 but with no significant sequence homology. IL-15 also stimulates human B cells to proliferation and immunoglobulin secretion. We measured serum levels of IL-15 in 84 HIV-1-infected individuals at different stages of disease in reference to 41 healthy blood donors. Our results show a marked elevation of IL-15 serum levels during HIV-1 infection. Moreover, we found that this increase correlated with serum levels of IgG (r ¼ 0 : 376; P < 0 : 0001), and partly with serum IgM (r ¼ 0 : 265; P ¼ 0 : 015). A significant increase of IL-15 production by cultured peripheral blood mononuclear cells (PBMC) and purified monocytes in the presence of HIV-1 virus suggests that monocytes/macrophages may be a source of higher IL-15 serum levels in HIV-1-infected individuals. These findings indicate a participation of IL-15 in the hypergammaglobulinaemia frequently associated with HIV-1 infection.