Correlation of Temperature and Toxicity in Murine Studies of Staphylococcal Enterotoxins and Toxic Shock Syndrome Toxin 1

Stiles, Bradley G.; Campbell, Yvette; Castle, Robert M.; Grove, Sara A.

doi:10.1128/iai.67.3.1521-1525.1999

Cited by 56 publications

(29 citation statements)

References 40 publications

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“…In concordance with human data, there is a good correlation between increased serum levels of IL-1, IL-2, TNF , and/or IFN with SEA-, SEB-, or TSST-1-induced shock in mice [148][149][150][151][152][153][154][155][156][157][158][159][160]. These efforts coincide with others involving SEA and genetic knockout mice deficient in IFN or the p55 receptor for TNF [141]. In addition to potentiation of SE effects in mice by other compounds, it has been recently reported that C3H/HeJ mice (non-LPS responders) lethally respond to one or two timed doses of SEB (seven micrograms total) given intranasally [166].…”

Section: Animal Models For Ses and Tsst-1: Necessary Steps Toward A Bsupporting

confidence: 80%

“…However, incubation of a human colonic monolayer (T84 cells) with SEB and peripheral blood mononuclear cells (PBMC) increases ion flow across the cell-based barrier, thus suggesting indirect toxin effects upon gut mucosa via the immune system and released proinflam-matory cytokines [140]. A cytokine protective against various bacterial superantigens in vivo, IL-10 (but not IL-4), dose-dependently inhibits permeability of T84 cell monolayers in vitro when added before or concomitantly with SEB [135,[140][141][142].…”

Section: In Vivo Effects Of Ses and Tsst-1: A Multifactorial Eventmentioning

confidence: 99%

“…influenza or lymphocytic choriomeningitis) amplify the toxic effects of superantigens in mice. Many of our studies involve an LPSpotentiated mouse model [104,141,150], as various in vitro and in vivo assays reveal a natural synergy (many log-fold) between SEs / TSST-1 and LPS [157][158][159][160][161][162]. As little as two micrograms of LPS alone in humans can cause endotoxic shock [163], thus only picogram quantities of endotoxin in conjunction with a superantigen can cause quite severe, lifethreatening effects [164].…”

Section: Animal Models For Ses and Tsst-1: Necessary Steps Toward A Bmentioning

confidence: 99%

See 2 more Smart Citations

Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire

Larkin¹,

Carman²,

Krakauer³

et al. 2009

CMC

121

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Staphylococcus aureus is a facultative, Gram-positive coccus well known for its disease-causing capabilities. In particular, methicillin and vancomycin resistant strains of S. aureus (MRSA and VRSA, respectively) isolated globally represent daunting medical challenges for the 21(st) Century. This bacterium causes numerous illnesses in humans such as food poisoning, skin infections, osteomyelitis, endocarditis, pneumonia, enterocolitis, toxic shock, and autoimmune disorders. A few of the many virulence factors attributed to S. aureus include antibiotic resistance, capsule, coagulase, lipase, hyaluronidase, protein A, fibronectin-binding protein, and multiple toxins with diverse activities. One family of protein toxins is the staphylococcal enterotoxins (SEs) and related toxic shock syndrome toxin-1 (TSST-1) that act as superantigens. There are more than twenty different SEs described to date with varying amino acid sequences, common conformations, and similar biological effects. By definition, very low (picomolar) concentrations of these superantigenic toxins activate specific T-cell subsets after binding to major histocompatibility complex class II. Activated T-cells vigorously proliferate and release proinflammatory cytokines plus chemokines that can elicit fever, hypotension, and other ailments which include a potentially lethal shock. In vitro and in vivo models are available for studying the SEs and TSST-1, thus providing important tools for understanding modes of action and subsequently countering these toxins via experimental vaccines or therapeutics. This review succinctly presents the pathogenic ways of S. aureus, with a toxic twist. There will be a particular focus upon the biological and biochemical properties of, plus current neutralization strategies targeting, staphylcoccocal superantigens like the SEs and TSST-1.

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Section: Animal Models For Ses and Tsst-1: Necessary Steps Toward A Bsupporting

confidence: 80%

Section: In Vivo Effects Of Ses and Tsst-1: A Multifactorial Eventmentioning

confidence: 99%

Section: Animal Models For Ses and Tsst-1: Necessary Steps Toward A Bmentioning

confidence: 99%

See 1 more Smart Citation

Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire

Larkin¹,

Carman²,

Krakauer³

et al. 2009

CMC

121

View full text Add to dashboard Cite

show abstract

“…[13][14][15] It appears that SEA is more potent than other toxin serotypes such as staphylococcal enterotoxin B (SEB) or staphylococcal enterotoxin C 1 (SEC 1 ). 13 Although LPS enhances the lethality of SEA in vivo, [13][14][15][16] the mechanism underlying the synergistic induction of pro-inflammatory cytokine responses remains unclear. In earlier studies, binding of SE to MHC class II molecules on monocytes resulted in an increase in IL-1 and TNFa.…”

Section: Introductionmentioning

confidence: 99%

Staphylococcal enterotoxin A induction of pro‐inflammatory cytokines and lethality in mice is primarily dependent on MyD88

et al. 2010

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SummaryStaphylococcal enterotoxin (SE) -induced toxic shock is triggered by inflammatory cytokine signal amplification after SE binding to major histocompatibility complex class II molecules on antigen-presenting cells and T-cell receptors. Identifying host cellular elements contributing to this pro-inflammatory signal amplification is critical for developing a strategy for therapeutic intervention. Myeloid differentiation primary-response protein 88 (MyD88) is an intracellular signalling adaptor protein primarily known for mediating pro-inflammatory cytokine responses. We investigated the role of MyD88 in staphylococcal enterotoxin A (SEA) -treated cell cultures and mouse models of toxic shock. Our results demonstrated that elevated levels of tumour necrosis factor-a, interferon-c, interleukin1a/b (IL-1a/b), IL-2 and IL-6 production correlated with up-regulation of MyD88 after treatment of spleen cells and mice with SEA alone or in combination with lipopolysaccharide (LPS). The SEA-induced lethality was also observed in (LPS-independent) D-galactosamine-sensitized mice.While LPS potentiated SEA-induced cytokine responses, D-galactosamine treatment had no additive effect. Most importantly, our results demonstrated that MyD88 )/) mice were resistant to SEA-induced toxic shock and had reduced pro-inflammatory cytokine responses. These results suggest that SEA-induced lethality is primarily dependent on MyD88. Our findings offer an important insight on potential therapeutic treatment of SEA-induced toxic shock targeting MyD88.Keywords: cytokine; D-galactosamine; knockout; lipopolysaccharides; myeloid differentiation primary-response protein 88; staphylococcal enterotoxin ANo claim to original US government works. 516Journal Compilation Ó 2010 Blackwell Publishing Ltd, Immunology, 130, 516-526 I M M U N O L O G Y O R I G I N A L A R T I C L Eon monocytes resulted in an increase in IL-1 and TNFa. 17 The SEB-dependent induction of IL-1 and TNF-a was thought to involve protein kinase C and protein tyrosine kinase. [17][18][19] Recent results indicate that IFN-c as well as IL-1 rely on myeloid differentiation factor 88 (MyD88) -dependent pathways. 20 The adaptor protein MyD88 integrates and transduces intracellular signals generated by the TLR and interleukin receptor (IL-R) superfamily, critically regulating innate immunity and host defence. 21,22 However, the impact of MyD88-mediated signalling with respect to toxic shock remains unknown.Conventionally, agonists (bacterial components) binding to host innate immune receptors, IL-1R, and all of the TLRs (excluding TLR3) prompt recruitment of the Toll-interleukin receptor (TIR) domain-containing adaptor molecule MyD88 through a TIR-TIR domain interaction. This interaction leads to downstream nuclear factor-jB (NF-jB) activation which permits the transactivation of pro-inflammatory cytokine genes. [23][24][25] With regard to TLR and MyD88 signalling in human monocytes, it has been reported that ligation of MHC class II with SEB up-regulates monocyte membrane TLR4 expressi...

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“…In murine studies [41] in vivo, levels of TNF‐α increase appreciably in response to superantigen stimulation. Studies [42,43] using TNF inhibition or TNF receptor knockout mice have shown that development of clinical TSS from staphylococcal enterotoxin may be inhibited.…”

Section: Superantigensmentioning

confidence: 99%

Toxic Shock Syndrome

Dellaripa¹

2000

J Intensive Care Med

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Toxic shock syndrome (TSS) represents a heterogeneous group of disorders that results in hypotension, multiorgan system involvement, and a characteristic rash or soft tissue infection caused by staphylococcal or streptococcal exotoxins and enterotoxins. Staphylococcal TSS emerged in the late 1970s as an illness associated with highly absorbent tampons; subsequently it has been described with postoperative infections, burns, and various viral illnesses. Although the morbidity rate associated with staphylococcal TSS may be high, the mortality rate approximates 5%. Streptococcal TSS has emerged in the 1980s and into the 1990s as a disorder that results in rapid progression of soft tissue infection in the form of cellulitis, myositis, or necrotizing fasciitis due to pyogenic streptococcal group A exotoxin. The rapidity of progression of local infection to hypotension and multiorgan failure results in a mortality rate of 30–70%. In both forms of TSS, staphylococcal and streptococcal exotoxins function as superantigens, a unique mechanism of immune activation that results in an exuberant T‐cell response and profound cytokine expression. The role of antibiotics is reviewed. The use of clindamycin in streptococcal TSS and the potential therapeutic role of intravenous immunoglobulin in both forms of this disorder are discussed as well.

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Correlation of Temperature and Toxicity in Murine Studies of Staphylococcal Enterotoxins and Toxic Shock Syndrome Toxin 1

Cited by 56 publications

References 40 publications

Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire

Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire

Staphylococcal enterotoxin A induction of pro‐inflammatory cytokines and lethality in mice is primarily dependent on MyD88

Toxic Shock Syndrome

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