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EN
In Staphylococcus aureus, 19 different superantigens (SAgs) have been described. Their genes are all located on mobile genetic elements, such as pathogenicity islands, plasmids, and phages. SAgs bypass conventional antigen recognition by directly cross-linking major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells with T cell receptors. This leads to massive T cell proliferation and cytokine release, which may end in toxic shock syndrome. The role of SAgs in other forms of sepsis is less well defined. In animal models, SAgs and lipopolysaccharide (LPS) very efficiently synergize in the induction of lethal shock, and on the basis of these observations a two-hit model of sepsis has been proposed: LPS or another monocyte stimulus hits first, then SAg or another T cell stimulus hits. In clinical studies, however, evidence for an involvement of SAgs in sepsis has been difficult to obtain. This may have a number of reasons: differences between humans and rodents in their response to LPS and SAg, heterogeneity of SAg combinations in S. aureus clinical isolates, lack of tools to analyze SAg effects in patients, blocking anti-SAg serum antibodies, and MHCII polymorphisms.
EN
We asked whether in atopic dermatitis (AD) increased T cell apoptosis in staphylococcal enterotoxin B (SEB)-activated cultures of peripheral blood mononuclear cells (PBMCs) is characteristic of the exacerbation of the disease or connected with skin colonization by Staphylococcus aureus. The clinical status of the patients was evaluated using the SCORAD index. The number of bacteria colonizing patients' skin lesions was determined by the cfu method. Mononuclear cells isolated from peripheral blood were stimulated by SEB and the apoptosis of CD3+ cells in culture was determined by flow cytometry using the monoclonal antibody APO2.7. The cytokine production in the culture supernatants was determined by ELISA and Cytometric Bead Array kits. T cell apoptosis was increased, while the production of interferon (IFN)-? was reduced in cultures of PBMCs of AD patients during exacerbation. The proportion of CD3+APO2.7+ cells positively correlated with the density of S. aureus recovered from skin lesions, but not with SCORAD index. By contrast, SCORAD index, but not S. aureus density, negatively correlated with IFN-? production. Furthermore it was found that the presence of S. aureus on uninvolved skin distinguishes a group of severe cases with high serum IgE level, increased T cell apoptosis, and reduced production of tumor necrosis factor ? in SEB- -stimulated cultures. Among AD patients the increased activation-induced T cell apoptosis observed in SEB- -stimulated cultures is related to skin colonization by S. aureus. The presence of bacteria on uninvolved skin is a feature of a distinct group of AD patients.
EN
Use of experimental models of staphylococcal infections clarified several bacterial virulence factors as well as many hematopoetic cell types and their products that are involved in the pathogenesis of infection. For many decades it has been believed that antibody mediated response to staphylococci and their products was the major, if not the only one, hallmark of immune reactivity during infection. Recent studies have documented that T cell mediated responses to superantigens produced by staphylococci are not only prominent but also decisive with respect to sequels. Also the nonantigen specific immune responsiveness to staphylococcal infection is reviewed including roles of neutrophils, complement system and nitric oxide. The knowledge gained regarding staphylococcal virulence factors and the host immune responses has prompted researchers to develop new strategies how to interact in vivo witl the infectious process. Some of these approaches are commented in this review regarding e. g. vaccination procedures in order to prevent severe infections as well as therapeutic procedures to minimize organ damage during an ongoing infectious process.
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