8. Danner R L, Elin RJ, Hosseini JM, Wesley RA, Reilly JM, et al. (1991) Endotoxemia in human septic shock. Chest 99: 169–175. 9. Azuma K, Koike K, Kobayashi T, Mochizuki T, Mashiko K, et al. (2004) Detection of circulating superantigens in an intensive care unit population. Int J Infect Dis 8: 292–298. 10. Kissner TL, Cisney ED, Ulrich RG, Fernandez S, Saikh KU (2010) Staphylococcal enterotoxin A induction of pro-inflammatory cytokines and lethality in mice is primarily dependent on MyD88. Immunology 130: 516–526. 11. Kissner TL, Ruthel G, Cisney ED, Ulrich RG, Fernandez S, et al. (2011) MyD88-dependent pro-inflammatory cytokine response contributes to lethal toxicity of staphylococcal enterotoxin B in mice. Innate Immunity 17: 451–462. 12. Kissner TL, Ruthel G, Alam S, Ulrich RG, Fernandez S, et al. (2011) Activation of MyD88 signaling upon staphylococcal enterotoxin binding to MHC class II molecules. PLoS ONE 6: e15985. 13. Liu X, Zhan Z, Li D, Xu L, Ma F, et al. (2011) Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol 12: 416–424. 14. Hassan GS, Mourad W (2011) An unexpected role for MHC class II. Nat Immunol 12: 375–376. 15. Akira S, Takeda K (2004) Toll-like receptor signaling. Nat Rev Immunol 4: 499– 511. 16. O’Neill LAJ (2003) The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochem Soc Trans 31: 643–647. 17. Sun D, Ding A (2006) MyD88-mediated stabilization of interferon-gamma- induced cytokine and chemokine mRNA. Nat Immunol 7: 375–381. 18. Cook DN, Pisetsky DS, Schwartz DA (2004) Toll-like receptors in the pathogenesis of human diseases. Nat Immunol 5: 975–979. 19. Kissner TL, Moisan L, Mann E, Alam S, Ruthel G, et al. (2011) A small molecule that mimics the BB-loop in the Toll/IL-1 receptor domain of MyD88 attenuates staphylococcal enterotoxin B induced pro-inflammatory cytokine production and toxicity in mice. J Biol Chem 286: 31385–31396. 20. Davis CN, Mann E, Behrens MM, Gaidarova S, Rebek M, et al. (2006) MyD88- dependent and –independent signaling by IL-1 in neurons probed by bifunctional Toll/IL-1 receptor domain/BB-loop mimetics. Proc Natl Acad Sci USA 103: 2953–2958. 21. Nallamsetty S, Austin BP, Penrose KJ, Waugh DS (2005) Gateway vectors for the production of combinatorially-tagged His6-MBP fusion proteins in the cytoplasm and periplasm of Escherichia coli. Protein Sci 14: 2964–2971. Inhibition of SEB Intoxication by a MyD88 Mimetic 22. Tropea JE, Cherry S, Waugh DS (2009) Expression and purification of soluble His (6)-tagged TEV protease. Methods Mol Biol 498: 297–307. 23. Xu Y, Tao X, Shen B, Horng T, Medzhitov R, et al. (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408: 111–115. 24. Nyman T, Stenmark P, Flodin S, Johansson I, Hammarstrom M, et al. (2008) The crystal structure of the human toll-like recptor 10 cytoplasmic domain reveals a putative signaling dimer. J Biol Chem 283:11861–11865. 25. Chan SI, Low LY, Hsu S, Li S, Liu T, et al. (2009) Molecular mimicry in innate immunity: crystal structure of a bacterial TIR domain. J Biol Chem 284: 21386– 21392. 26. Burns K, Martinon F, Esslinger C, Pahl H, Schneider P, et al. (1998) MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 273: 12203– 12209. 27. Basith S, Manavalan B, Govindaraj RG, Choi S (2011) In silico approach to inhibition of signaling pathways of Toll-like receptors 2 and 4 by ST2L. PLoS One 6: e23989. 28. Piani A, Hossle JP, Birchler T, Siegrist CA, Heumann D, et al. (2000) Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness. Eur J Immunol 30: 3140–3146. 29. Frei R, Steinle J, Birchler T, Loeliger S, Roduit C, et al. (2010) MHC class II molecules enhance Toll-like receptor mediated innate immune responses. PLoS One 5: e8808. 30. Al-Daccak R, Mooney N, Charron D (2004) MHC class II signaling in antigen presenting cells. Curr Opin Immunol 16: 108–113. 31. Gabhann JN, Jefferies CA (2011) TLR-induced activation of Btk-role for endosomal MHC class II molecules revealed. Cell Res 21: 998–1001. 32. Hopkins PA, Fraser JD, Pridmore AC, Russell HH, Read RC, et al. (2005) Superantigen recognition by HLA class II on monocytes up-regulates toll-like receptor 4 and enhances proinflammatory responses to endotoxin. Blood 105: 3655–3662. 33. Dunne A, O’Neill LA (2003) The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003: re3. 34. Beno DW, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, et al. (2001) Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catherized rats. Am J Physiol Gastrointest Liver Physiol 280: G866– G872. PLoS ONE | www.plosone.org 12 July 2012 | Volume 7 | Issue 7 | e40773