The Innate Immune System Is Activated by Stimulation of Vaginal Epithelial Cells with<i>Staphylococcus aureus</i>and Toxic Shock Syndrome Toxin 1

Peterson, Marnie L.; Ault, Kevin A.; Kremer, Mary; Klingelhutz, Aloysius J.; Davis, Catherine; Squier, Christopher A.; Schlievert, Patrick M.

doi:10.1128/iai.73.4.2164-2174.2005

Cited by 98 publications

(210 citation statements)

References 64 publications

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“…We have not tested GML effects when administered intravenously, but significant inhibition of signal transduction may preclude its use systemically. Finally, the inhibition of inflammatory cytokine and chemokine production as was observed in the case of inhibition of superantigen effects on T cells, macrophages, and vaginal epithelial cells, suggests GML may function also generally as a topical anti-inflammatory agent (36). Effect of GML on superantigenicity of TSST-1 (1 ug/ml, □), SPE A (1 ug/ml, ■), and SEB (1 ug/ml, △).…”

Section: Discussionmentioning

confidence: 83%

“…Our prior studies suggested that TSS is initiated by low-level inflammation produced by S. aureus and exotoxin activation of HVECs to release chemokines and cytokines through inflammation which facilitates superantigen transport across the mucosal barrier (36). GML was highly effective in preventing the release of chemokines and cytokines by HVECs in response to stimulation with TSST-1, SEB, and SPE A, probably through inhibition of signal transduction through an unknown HVEC receptor.…”

Section: Discussionmentioning

confidence: 98%

“…These superantigens were previously determined to stimulate chemokine and cytokine production from HVECs (36). The 100 ug/ml dose of all superantigens was chosen because our unpublished observations indicate that TSST-1 and SEB-positive S. aureus strains make up to 1000 ug/ml of exotoxin when cultured for 8 h in biofilms (as might be expected to occur in vivo); we used a 10-fold lower dose.…”

Section: Inhibition Of Human Vaginal Epithelial Cell (Hvec) Cytokine mentioning

confidence: 99%

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Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

Peterson

Schlievert

2006

Biochemistry

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Many exotoxins of gram positive bacteria, such as superantigens (staphylococcal enterotoxins, toxic shock syndrome toxin-1 [TSST-1], and streptococcal pyrogenic exotoxins) and anthrax toxin are bioterrorism agents that cause diseases by immunostimulation or cytotoxicity. Glycerol monolaurate (GML), a fatty acid monoester found naturally in humans, has been reported to prevent synthesis of gram positive bacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammalian cells and prevent rabbit lethality from TSS. GML (≥10 ug/ml) inhibited superantigen (5 ug/ml) immunoproliferation, as determined by inhibition of 3 H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 × 10 6 cells/ml) as well as phospholipase Cγ1, suggesting inhibition of signal transduction. The compound (20 ug/ml) prevented superantigen (100 ug/ml) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 ug) inhibited rabbit lethality due to TSST-1 administered vaginally. GML (10 ug/ml) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal α and β) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was non-toxic to mammalian cells (up to 100 ug/ml) and rabbits (250 ug). GML stabilized mammalian cell membranes, as erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0 to 0.05 M saline) or staphylococcal α and β-hemolysins when erythrocytes were pretreated with GML. GML may be useful in management of gram positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.Many gram positive bacterial pathogens produce exotoxins that are potential agents of bioterrorism and contribute to their abilities to cause human diseases (1-3). Examples include anthrax toxin made by Bacillus anthracis (2), superantigens produced by Staphylococcus aureus, including staphylococcal enterotoxins (SEs) 1 and toxic shock syndrome toxin-1 (TSST-1) (1), and superantigens produced by group A streptococci, including streptococcal pyrogenic exotoxins (SPEs) (3). Other exotoxins, such as staphylococcal α and β-hemolysins and streptolysins, are not agents of bioterrorism but have adjunct roles in virulence and can be used as model toxins to study mechanisms of cellular toxicity.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Section: Inhibition Of Human Vaginal Epithelial Cell (Hvec) Cytokine mentioning

confidence: 99%

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Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

Peterson

Schlievert

2006

Biochemistry

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“…Our rationalization of the two-fold cutoff was based on the fact that a 1.5-to 2.0-fold cutoff appears to ensure reproducibility and accuracy of microarray-based data and has been used by several other research groups in recent studies. [18][19][20][21] Hence, we identified a total of 329 genes that were increased in expression and a total of 76 genes were decreased in expression in response to IFN-g. Not surprisingly, prominent among the genes found to be stimulated were those related to immune function, including immune effectors such as chemokine and major histocompatibility complex (MHC) genes along with those identified in Table 1. With a more detailed analysis of the genes altered in expression, we were able to provide a better foundation for understanding the molecular response of human microglia to one of the principal proinflammatory cytokines, IFN-g.…”

Section: Data Summarymentioning

confidence: 99%

Transcriptional response of human microglial cells to interferon-γ

Rock

Deshpande

et al. 2005

Genes Immun

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Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-g, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-g treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-g signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-g induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-g-a key to understanding cell-mediated immunity of the CNS.

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“…Since the toxin was introduced on mucosal surfaces, the only method for systemic activation would be if the toxin crossed the epithelial cell barrier and gained access to the body. Vaginal epithelial cells were also shown to bind TSST-1 and induce TNF production while treatment of epithelial cells with TSST-1 or SEB induced production of MIP-3 and IL-8 (Brosnahan et al, 2001;Peterson, et al, 2005). SE-induced shock causes severe damage to the endothelial vasculature and vascular leak contributes significantly to TSS pathology (Krakauer, 1994;Ortega et al 2010).…”

Section: Toxic Shock Syndromementioning

confidence: 99%

Staphylococcal Enterotoxins, Stayphylococcal Enterotoxin B and Bioterrorism

Hale¹

2012

Bioterrorism

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The Innate Immune System Is Activated by Stimulation of Vaginal Epithelial Cells withStaphylococcus aureusand Toxic Shock Syndrome Toxin 1

Cited by 98 publications

References 64 publications

Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

Transcriptional response of human microglial cells to interferon-γ

Staphylococcal Enterotoxins, Stayphylococcal Enterotoxin B and Bioterrorism

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