Bacterial superantigens

Proft, Thomas; Fraser, John D.

doi:10.1046/j.1365-2249.2003.02203.x

Cited by 390 publications

(350 citation statements)

References 81 publications

Supporting

Mentioning

336

Contrasting

Unclassified

Order By: Relevance

“…Although the precise mechanism of action of JWH-015 was unknown, the authors suggested that JWH-015 and other cannabinoids may decrease the number of CD4 + T cells thereby enhancing the myelin repair. Bacterial superantigens are considered to be the most powerful T cell activators [38]. Thus, exposure to such superantigens results in a dramatic induction of cytokines and consequent fever, shock and death.…”

Section: Discussionmentioning

confidence: 99%

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Lombard

Nagarkatti

2007

Clinical Immunology

105

View full text Add to dashboard Cite

Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2 selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.

show abstract

Section: Discussionmentioning

confidence: 99%

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Lombard

Nagarkatti

2007

Clinical Immunology

105

View full text Add to dashboard Cite

show abstract

“…SSL7 (formerly named SET1) is the first described member of a new family of putative S. aureus toxins, the staphylococcal superantigen-like (SSL) proteins (11,12), related to the staphylococcal enterotoxins (SEs) or superantigens (13). The SSL proteins have Ϸ30% sequence identity with toxic shock syndrome 1 (TSST-1) and 25% or less identity with other SEs.…”

mentioning

confidence: 99%

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1

Ramsland

Willoughby

Trist

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

106

102

View full text Add to dashboard Cite

Infection by Staphylococcus aureus can result in severe conditions such as septicemia, toxic shock, pneumonia, and endocarditis with antibiotic resistance and persistent nasal carriage in normal individuals being key drivers of the medical impact of this virulent pathogen. In both virulent infection and nasal colonization, S. aureus encounters the host immune system and produces a wide array of factors that frustrate host immunity. One in particular, the prototypical staphylococcal superantigen-like protein SSL7, potently binds IgA and C5, thereby inhibiting immune responses dependent on these major immune mediators. We report here the three-dimensional structure of the complex of SSL7 with Fc of human IgA1 at 3.2 Å resolution. Two SSL7 molecules interact with the Fc (one per heavy chain) primarily at the junction between the C␣2 and C␣3 domains. The binding site on each IgA chain is extensive, with SSL7 shielding most of the lateral surface of the C␣3 domain. However, the SSL7 molecules are positioned such that they should allow binding to secretory IgA. The key IgA residues interacting with SSL7 are also bound by the leukocyte IgA receptor, Fc␣RI (CD89), thereby explaining how SSL7 potently inhibits IgAdependent cellular effector functions mediated by Fc␣RI, such as phagocytosis, degranulation, and respiratory burst. Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely to facilitate survival in mucosal environments such as the nasal passage and may contribute to systemic infections.Staphylococcus aureus is an important human pathogen causing conditions ranging from minor superficial skin infections to life-threatening syndromes, including sepsis, toxic shock syndrome, osteomyelitis, pneumonitis, and endocarditis. It is carried without symptoms in at least 20% of individuals (1, 2). The emergence in the 1960s of pandemic penicillin-resistant S. aureus has been followed by a variety of hospital-associated and community-associated methicillin-resistant strains (HA-and CA-MRSA) (2, 3). The increased prevalence of MRSA infections and corresponding rise in life-threatening syndromes have made it imperative to elucidate the mechanisms of pathogenesis for S. aureus. The interaction between S. aureus and the host is complex and is mediated by an array of bacterial proteins that both mediate the various pathologies and modify the immune system of the host (4-10).SSL7 (formerly named SET1) is the first described member of a new family of putative S. aureus toxins, the staphylococcal superantigen-like (SSL) proteins (11, 12), related to the staphylococcal enterotoxins (SEs) or superantigens (13). The SSL proteins have Ϸ30% sequence identity with toxic shock syndrome 1 (TSST-1) and 25% or less identity with other SEs. Despite the sequence differences, the SSL proteins have a typical SE tertiary structure consisting of a distinct oligonucleotide/oligosaccharide binding (OB-fold) linked to a ␤-grasp domain (14 -16).Similar to the se genes, the ssl genes are located in a pathogenicity island (SaPIn2) and ...

show abstract

“…The bestcharacterized bacterial SAgs are produced by S. aureus and by a related disease-causing bacteria, Streptococcus pyogenes. Bacterial genome sequencing has revealed that there is a large number of genetically distinct SAgs produced by these organisms, with more than 30 different serotypes 4 . S. aureus secretes the staphylococcal enterotoxins (SEs) and the toxic shock syndrome toxin-1 (TSST-1), whereas S. pyogenes secretes the streptococcal pyrogenic exotoxins (SPEs).…”

mentioning

confidence: 99%

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

et al. 2010

View full text Add to dashboard Cite

superantigens (sAgs) are bacterial toxins that interact with immunoreceptors, T cell receptor (TCR) and major histocompatibility complex (mHC) class II, conventionally through the variable β-domain of TCR (TCRVβ). They induce a massive release of cytokines, which can lead to diseases such as food poisoning and toxic shock syndrome. In this study, we report the X-ray structure of the ternary complex between staphylococcal enterotoxin H (sEH) and its human receptors, mHC class II and TCR. The structure demonstrates that sEH predominantly interacts with the variable α-domain of TCR (TCRVα), which is supported by nuclear magnetic resonance (nmR) analyses. Furthermore, there is no contact between mHC and TCR upon complex formation. structural analyses suggest that the major contact points to TCRVα are conserved among other bacterial sAgs. Consequently, a new dimension of sAg biology emerges, suggesting that in addition to the conventional interactions with the TCRVβ domain, sAgs can also activate T cells through the TCRVα domain.

show abstract

Bacterial superantigens

Cited by 390 publications

References 81 publications

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

Contact Info

Product

Resources

About