Evolving superantigens of Staphylococcus aureus

Ulrich, R

doi:10.1016/s0928-8244(99)00139-x

Cited by 24 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Microorganisms, such as the pathogenic bacterium S. aureus, have surface proteins that can modulate the host immune system. S. aureus expresses superantigens (SAgs), which bind to human MHC class II molecules, primarily HLA-DR, and TCR (31)(32)(33)(34)(35). SAg binding to human T lymphocytes alone can inappropriately activate the cells, and this can result in T cell anergy or the elimination of the activated cells by apoptosis (36 -38).…”

Section: Discussionmentioning

confidence: 99%

Fibronectin Binding Protein A of Staphylococcus aureus Can Mediate Human T Lymphocyte Adhesion and Coactivation

Miyamoto

Wann

Fowler

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The extracellular matrix protein fibronectin (FN) mediates the adhesion of bacteria as well as T lymphocytes. Mammalian cells express integrins α4β1 and α5β1 as the major FN-binding cell surface receptors. Bacteria such as Staphylococcus aureus, also express FN-binding receptors that are important for adherence to host tissue and initiation of infection. The S. aureus FN-binding protein, FnbpA, has been previously identified, and recombinant proteins that correspond to distinct functional regions of this protein have been made. Three recombinant truncated forms of FnbpA, rFnbpA(37-881), rFnbpA(37-605), and rFnbpA(620-881), were examined for effects on in vitro adhesion and coactivation of human T lymphocytes. These proteins, when coimmobilized with anti-CD3 mAb, activated T lymphocyte proliferation. The coactivation signal generated by the rFnbpA proteins required medium containing serum with FN. Furthermore, the costimulatory signal could be restored in FN-depleted serum when the rFnbpAs were preloaded with soluble FN. Monoclonal Ab blocking studies revealed that integrin α5β1 is the major receptor responsible for the rFnbpA costimulatory signal. Shear flow cell detachment assays confirmed that lymphocytes can bind to FN captured by the rFnbpA proteins. These results suggest that the S. aureus rFnbpA can interact with integrin α5β1 via an FN bridge to mediate adhesion and costimulatory signals to T lymphocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Fibronectin Binding Protein A of Staphylococcus aureus Can Mediate Human T Lymphocyte Adhesion and Coactivation

Miyamoto

Wann

Fowler

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Superantigens are secreted proteins that aid in immune evasion and cause severe pathophysiological changes in the host, often leading to shock. As superantigen-activated T cells are deleted by apoptosis or become nonresponsive (anergic) to restimulation, superantigens are often used to study inducible tolerance (33).…”

Section: Cd4mentioning

confidence: 99%

Mycobacterium bovisBCG-Infected Mice Are More Susceptible to Staphylococcal Enterotoxin B-Mediated Toxic Shock than Uninfected Mice despite Reduced In Vitro Splenocyte Responses to Superantigens

et al. 2002

View full text Add to dashboard Cite

Type 1 T-cell responses against intracellular pathogens play a crucial role in mediating protection. We examined whether the induction of a strong type 1 T-cell response during a chronic bacterial infection influences responses to superantigens capable of inducing acute shock. Intravenous infection of mice with Mycobacterium bovis BCG appeared to induce a progressive anergy towards staphylococcal enterotoxin B (SEB) and towards antigen preparation of BCG (BCG-Ag) itself, based on diminished gamma interferon (IFN-␥) production by SEB-and BCG-Ag-stimulated splenocytes from infected mice. In contrast to these in vitro results, injection of SEB into BCG-infected mice led to a dramatic increase in the serum IFN-␥ levels and the death of infected but not of control mice. In vitro hyporesponsiveness towards SEB and BCG-Ag occurred only with unfractionated splenocyte cultures, as purified T cells from infected mice produced higher levels of IFN-␥. Hyporesponsiveness towards SEB and BCG-Ag in unfractionated splenocyte cultures was not due to suppressive antigen-presenting cells (APCs), as APCs from infected mice stimulated higher levels of IFN-␥ from purified T cells. The diminished IFN-␥ levels observed with bulk splenocytes appear to be due to changes in the T-cell-to-APC ratio that result in a decreased proportion of T cells, coupled to reduced proliferative responses and an increased susceptibility of effector T cells to activation-induced cell death in vitro. Our results indicate that the reported phenomena of T-cell anergy during mycobacterial infection may be an in vitro consequence of the development of a strong type 1 response in vivo. CD4ϩ -and CD8 ϩ -T-cell activation is important for protection against infectious diseases (23). Under extreme polarizing conditions (such as chronic infections), CD4ϩ T cells differentiate into type 1 (producing interleukin 2 [IL-2] and gamma interferon [IFN-␥]) or type 2 (producing IL-4, IL-5, and IL-13) effectors and, once generated, mediate differential protection depending on the type of pathogen and the strain of mouse used (23). CD8 ϩ T cells, on the other hand, are primarily involved in protection against intracellular pathogens, particularly those that replicate in the cytoplasm of the host cell (38).Mycobacterium bovis BCG is a facultative intracellular bacterium that causes chronic infections in susceptible hosts. In mice, infection with BCG results in the development of splenomegaly in the first 4 weeks of disease, with increased accumulation of splenocytes during that time (25). Infection also leads to the development of a BCG-specific IFN-␥ response at both the CD4 ϩ -and CD8 ϩ -T-cell levels (32). As with other pathogenic mycobacteria, BCG infection has been reported to induce T-cell anergy, particularly at higher bacterial burdens (25).Superantigens hyperstimulate T cells by acting as a bridge between superantigen-restricted V␤-containing T-cell receptors (TCRs) and major histocompatibility complex (MHC) class II molecules, resulting in a high responder frequency a...

show abstract

“…At extremely low concentrations, these molecules can induce profound disturbances in the homeostasis of the immune system (17,44). These toxins play a critical role in human toxic shock syndrome and food poisoning, but their possible role in the onsets or maintenance of other diseases is not well understood (41).…”

mentioning

confidence: 99%

Staphylococcus aureus Enterotoxin D Is Secreted in Milk and Stimulates Specific Antibody Responses in Cows in the Course of Experimental Intramammary Infection

2006

View full text Add to dashboard Cite

An enterotoxin D (SED)-producing strain of Staphylococcus aureus was used to infect one mammary gland of each of 17 lactating dairy cows. All glands became infected and shed bacteria over a sampling period of 3 weeks. Serum and milk antibodies specific for SED were monitored by an enzyme-linked immunosorbent assay for 12 weeks. Elevated anti-SED antibodies were detected in all cows after infection, and immunoglobulin of the G2 subclass comprised most of the specific serum response. SED was detected in mastitic milk samples from two cows at levels of 5 to 10 ng/ml. An in vitro lymphocyte proliferation assay showed that SED at levels below 10 pg/ml induced proliferation of bovine lymphocytes and that sheep antiserum specific for SED neutralized this proliferative response. Sera obtained from the cows pre-and postinfection inhibited lymphocyte proliferation at SED concentrations of 10 and 50 ng/ml, respectively. The addition of SED to whole blood or to isolated neutrophils had no significant effect on neutrophil function in vitro. The results show that SED is secreted during mammary gland infection, is mitogenic for bovine lymphocytes, and stimulates the production of specific antibodies.Staphylococcus aureus is a major cause of intramammary infection in ruminants and is a causative agent of a range of human and animal diseases. S. aureus mastitis tends to commence with an acute clinical episode which subsequently develops to become a chronic infection (1). The cure rate after antibiotic therapy is low (42). The chronic nature of bovine staphylococcal mastitis and the ability of the bacteria to withstand strong inflammatory responses may be associated with an impairment of the immune response mediated by factors secreted by S. aureus (39).S. aureus produces a family of related superantigens (SAgs) that includes several staphylococcal enterotoxins (SE) and toxicshock-syndrome toxin (TSST) variants (6). Staphylococcal SAgs are prototypical microbial superantigens, characterized by their ability to bind to major histocompatibility complex class II molecules and specific V␤ segments of ␣␤ T-cell receptors (32). SAgs bypass the antigenic specificities of T-cell receptors and stimulate abnormally large numbers of T cells. At extremely low concentrations, these molecules can induce profound disturbances in the homeostasis of the immune system (17, 44). These toxins play a critical role in human toxic shock syndrome and food poisoning, but their possible role in the onsets or maintenance of other diseases is not well understood (41).Geographical differences exist in the occurrence of SAg-producing strains causing mastitis (22). Kenny et al. (19) found that S. aureus strains producing enterotoxin D (SED) alone or in combination with S. aureus enterotoxin C (SEC) and TSST-1 accounted for 22% of the isolates from New York State. In Norway, a previous study showed that 58% of S. aureus isolates expressed SAgs and that the production of SEC and TSST-1 in combination predominated (40). Some reports have suggested that S. aureus...

show abstract

Evolving superantigens of Staphylococcus aureus

Cited by 24 publications

References 40 publications

Fibronectin Binding Protein A of Staphylococcus aureus Can Mediate Human T Lymphocyte Adhesion and Coactivation

Fibronectin Binding Protein A of Staphylococcus aureus Can Mediate Human T Lymphocyte Adhesion and Coactivation

Mycobacterium bovisBCG-Infected Mice Are More Susceptible to Staphylococcal Enterotoxin B-Mediated Toxic Shock than Uninfected Mice despite Reduced In Vitro Splenocyte Responses to Superantigens

Staphylococcus aureus Enterotoxin D Is Secreted in Milk and Stimulates Specific Antibody Responses in Cows in the Course of Experimental Intramammary Infection

Contact Info

Product

Resources

About