The bacterial superantigen and superantigen‐like proteins

Fraser, John D.; Proft, Thomas

doi:10.1111/j.1600-065x.2008.00681.x

Cited by 430 publications

(469 citation statements)

References 160 publications

Supporting

Mentioning

455

Contrasting

Unclassified

Order By: Relevance

“…In certain conditions, this immune activation can be robust, leading to a severe systemic cytokine storm (eg, TSS, Kawasaki disease, and neonatal TSS-like exanthematous disease 4,10,11 ). While SIRS leads to MODS and death, in the absence of prompt intervention, 3 the immunopathogenesis of this process is poorly understood because of lack of a robust animal model. The lack of a reliable animal model has also led to incomplete cellular and molecular characterization of TSS.…”

Section: Discussionmentioning

confidence: 99%

“…2 Important among them are the superantigen exotoxins. 3,4 Superantigens (SAgs) are the most potent naturally occurring biological activators of T lymphocytes. Unlike conventional antigens, unprocessed SAgs bind directly to cell surface major histocompatibility complex class II (MHC-II) molecules outside of the peptidebinding groove.…”

mentioning

confidence: 99%

“…Therefore, unlike conventional antigens, SAgs cause MHC-II-dependent, MHC-unrestricted, CD4 and CD8 co-receptor-independent, TCR V␤-specific but antigen-nonspecific T-cell activation. 3,5 Activated T cells produce a variety of cytokines and chemokines, which both directly and indirectly amplify this inflammatory cascade and trigger production of additional cytokines and chemokines from a variety of other sources. This process results in a massive cytokine/chemokine storm called systemic inflammatory response syndrome (SIRS), which ultimately leads to multiple-organ dysfunction syndrome (MODS) and culminates in high mortality if intervention is not prompt.…”

mentioning

confidence: 99%

“…6,7 S. aureus and S. pyogenes produce nearly 30 different SAgs. 3,4 While the mechanisms that regulate production of these exotoxins in vivo are not fully understood, several SAgs are produced in vivo after infection, and SAgs conSupported by NIH grant 1R01AI068741.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as D-galactosamine (D-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without D-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4 ؉ and CD8؉), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the D-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Therefore, superantigens bypass the specificity of conventional Ag recognition and can activate up to 20% of the total number of T cells (5). The massive activation of the adaptive immune system that ensues helps the pathogen to evade an appropriate immune response.…”

Section: G Lucocorticoids Bind the Glucocorticoid Receptor (Gr)mentioning

confidence: 99%

Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase Cβ2

Verhaar

Wildenberg

Duijvestein

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

The glucocorticoid receptor is present in a TCR-associated complex, which includes the Src family tyrosine kinase Lck. Glucocorticoids rapidly dissociate this complex, resulting in the inhibition of canonical Lck-phospholipase C (PLC)γ–dependent TCR signaling. The relative importance of this nongenomic role for the glucocorticoid receptor compared with its direct transcriptional effects is not known. Superantigens induce a state of steroid resistance in activated T cells. It was reported that, in addition to canonical Lck-PLCγ signaling, superantigens can activate a noncanonical G protein–PLCβ–dependent signaling pathway. In this study, we show that staphylococcal enterotoxin B activates a Gαq and PLCβ2–dependent pathway in human T cells. We find that this pathway bypasses the need for canonical Lck-PLCγ signaling in T cell activation and renders superantigen-stimulated T cells insensitive to glucocorticoids in vitro. We show that the PLCβ inhibitor U-73122 sensitizes staphylococcal enterotoxin B–treated mice to dexamethasone in vivo. In conclusion, we find that effects of glucocorticoids on TCR-induced T cell proliferation are mainly nongenomic and can be bypassed by the activation of an Lck-independent signaling pathway.

show abstract

Superantigens

Langley

Renno

2011

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Superantigens (SAgs) are microbial products that have the ability to promote massive activation of immune cells, leading to the release of inflammatory mediators that can ultimately result in hypotension, shock, organ failure and death. They achieve this by simultaneously binding and activating major histocompatibility complex class II molecules on antigen‐presenting cells and T‐cell receptors on T lymphocytes bearing susceptible Vβ regions. Why SAgs function in this manner is still not fully understood although it is thought that the resulting Th1 response may divert the immune system from effective microbial clearance and/or result in the cytokine‐mediated suppression and deletion of activated T cells. Many bacterial and viral species have adapted unrelated SAgs and this article will highlight some of the features of this diverse group of molecules, from the ways in which they interact with the host to the association of various SAgs with acute and chronic diseases. Key Concepts: Superantigens are toxins produced by many pathogenic bacteria and viruses. Superantigens are defined as molecules that bind to the major histocompatibility complex (MHC) class II and active T cells bearing a particular T‐cell receptor beta chain variable (Vβ) domain. Superantigens are implicated in inducing autoimmunity through the activation of autoreactive T cells that express particular Vβ elements. Superantigens are responsible for staphylococcal and streptococcal toxic shock. The superantigens of Staphylococcus aureus are responsible for staphylococcal food poisoning. The endogenous superantigen of the mouse mammary tumour virus (MMTV) causes deletion of T cells bearing a particular Vβ element, amplification of infected B cells and transmission of virus to the offspring.

show abstract

The bacterial superantigen and superantigen‐like proteins

Cited by 430 publications

References 160 publications

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase Cβ2

Superantigens

Contact Info

Product

Resources

About