July 11, 2018

By: douano@listlabs.com

By: Karen Crawford, PhD.
President, List Labs

Staphylococcal enterotoxin type B (SEB) is a powerful player in the family of toxins; in scientific terms, a superantigen.  This enterotoxin binds to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and specific V-β chains of the T-cell receptors.  This interaction between the three molecules leads to up-regulation of markers and proliferation of T-cells; additionally, it causes a massive release of proinflammatory cytokines including tumor necrosis factor (TNF), interleukins IL-1, IL-6 and interferon-gamma (INF-gamma) (1,2). SEB can form a complex with and activate T cell receptors even in the absence of MHC Class II antigens, making it a useful tool in stimulating T cells (3).

 

SEB Toxin’s Associations with Human Diseases

SEB is associated with staphylococcal food poisoning, along with TSST-1, is part of the toxic shock syndrome (4) and very likely has a role in human diseases such as atopic dermatitis (5) allergy and rhinitis (6) and the development of autoimmune diseases (7).  A mouse model to simulate Toxic Shock Syndrome has been created by exposing mice to both SEB and lipopolysaccharide (8).

Staphylococcal enterotoxin B is on the Centers for Disease Control and Prevention Select Agents & Toxins list, because of high toxicity and the potential to be aerosolized for wide dissemination; however, the quantity which a principal investigator can possess without registration is sufficient for research. Despite the toxicity and potential danger, SEB is a useful tool in research.

 

Some papers utilizing SEB toxin are described below:

Busbee et al (9) cultured splenocytes in 96-well plates in the presence and absence of SEB.  Supernatants were collected and analyzed for cytokine levels using ELISA kits purchased from Biolegend (San Diego, CA) for determining interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and IL-6.

Herter et al (10) investigated T cell movement between lymph nodes and sites of inflammation.  In this study, SEB is used extensively as a positive control, stimulating an immune response in the mouse kidney and in various cultured cells.

Janik and Lee (11) has used SEB in mice to develop an understanding of the inhibitory effect SEB may have on pre-existing immunity to pathogens unrelated to the superantigen.  These studies demonstrated that SEB in BALB/c mice selectively targets memory CD4 T cells.

 

References

1. Marrack P, Blackman M, Kushnir E, Kappler J (1990)The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells.J. Exp. Med. 171: 455–464.
2. Krakauer T and Stiles BG (2013) The staphylococcal enterotoxin (SE) family: SEB and siblings Virulence 4: 759-773. PMID: 23959032
3. Hewitt CR, Lamb JR, Hayball J, Hill M, Owen MJ, O’Hehir RE (1992) Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor. J Exp Med. 175:1493–1499. PMID: 1588277 
4. Kashiwada T, Kikuchi K, Abe S, Kato H, Hayashi H, Morimoto T, Kamio K et al (2012) Staphylococcal enterotoxin B toxic shock syndrome induced by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Intern. Med. 51: 3085–3088. PMID: 23124156
5. Breuer K, Wittmann M, Bosche B, Kapp A, Werfel T (2000)Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB). Allergy 55: 551–555. PMID: 10858986
6. Pastacaldi C, Lewis P, Howarth P (2011)Staphylococci and staphylococcal superantigens in asthma and rhinitis:  systematic review and meta-analysis. Allergy 66: 549–555. PMID: 21087214
7. Principato M, Qian BF (2014)Staphylococcal enterotoxins in the etiopathogenesis of mucosal autoimmunity within the gastrointestinal tract.Toxins 6: 1471–1489. PMID: 21535520
8. Huzella LM, Buckley MJ, Alves DA, Stiles BG, Krakauer T (2009) Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse model. Vet. Res. Sci. 86:241–247. PMID: 18793785
9.  BusbeePB, Nagarkatti M, Nagarkatti PS (2014) Naturalindoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression. Toxicol Appl Pharmacol. 274: 7–16 PMID: 24200994
10. Herter JM, Grabie N, Cullere X, Azcutia V, RosettI F, Bennett P, Herter-Sprie GS, Eylaman W, Luscinakas FW, Lichtman AH and Mayadas TN (2015) AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation. Nature Communications6, Art. No.: 10182. PMID: 26680259
11. Janik DK, Lee WT (2015) Staphylococcal Enterotoxin B (SEB) Induces Memory CD4 T Cell Anergy in vivoand Impairs Recall Immunity to Unrelated Antigens. J Clin Cell Immunol. 6(4):1-8. PMID: 26807307