Rapid clearance of the bacterial superantigen staphylococcal enterotoxin B in vivo.

1996 ◽  
Vol 64 (11) ◽  
pp. 4567-4573 ◽  
Author(s):  
R Vabulas ◽  
R Bittlingmaier ◽  
K Heeg ◽  
H Wagner ◽  
T Miethke
Keyword(s):  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Clearance ◽  
Enterotoxin B ◽  
Bacterial Superantigen

scholarly journals Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice.

1996 ◽  
Vol 183 (6) ◽  
pp. 2481-2488 ◽  
Author(s):  
H W Mittrücker ◽  
A Shahinian ◽  
D Bouchard ◽  
T M Kündig ◽  
T W Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Induction ◽  
Cd28 Costimulation ◽  
Enterotoxin B ◽  
Deficient Mice

We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of V beta 8+ T cells, but not for deletion. The lack of expansion was not due to a failure of SEB to activate V beta 8+ T cells, as V beta 8+ T cells from both CD28-/- and CD28+/+ mice showed similar phenotypic changes within the first 24 h after SEB injection and cell cycle analysis showed that an equal percentage of V beta 8+ T cells started to proliferate. However, the phenotype and the state of proliferation of V beta 8+ T cells was different at later time points. Furthermore, in CD28-/- mice injection with SEB led to rapid induction of unresponsiveness in SEB responsive T cells, indicated by a drastic reduction of proliferation after secondary SEB stimulation in vitro. Unresponsiveness could also be demonstrated in vivo, as CD28-/- mice produced only marginal amounts of TNF alpha after rechallenge with SEB. In addition CD28-/- mice were protected against a lethal toxic shock induced by a second injection with SEB. Our results indicate that CD28 costimulation is crucial for the T cell-mediated toxicity of SEB and demonstrate that T cell stimulation in the absence of CD28 costimulation induces unresponsiveness in vivo.

scholarly journals Potent Neutralization of Staphylococcal Enterotoxin B In Vivo by Antibodies that Block Binding to the T-Cell Receptor

2019 ◽  
Vol 431 (21) ◽  
pp. 4354-4367 ◽  
Author(s):  
Gang Chen ◽  
Hatice Karauzum ◽  
Hua Long ◽  
Danielle Carranza ◽  
Frederick W. Holtsberg ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B ◽  
Potent Neutralization

scholarly journals Measurement of Staphylococcal Enterotoxin B in Serum and Culture Supernatant with a Capture Enzyme-Linked Immunosorbent Assay

2007 ◽  
Vol 14 (9) ◽  
pp. 1094-1101 ◽  
Author(s):  
E. Cook ◽  
X. Wang ◽  
N. Robiou ◽  
B. C. Fries
Keyword(s):  
Immunosorbent Assay ◽  
Staphylococcal Enterotoxin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Staphylococcal Enterotoxin B ◽  
Low Concentrations ◽  
Life Threatening ◽  
Nasal Inhalation ◽  
Enterotoxin B ◽  
Rapid Binding

ABSTRACT Staphylococcal enterotoxin B (SEB) is a select agent because it is a potent mitogen that elicits life-threatening polyclonal T-cell proliferation and cytokine production at very low concentrations. Efforts are in progress to develop therapeutic reagents and vaccines that neutralize or prevent the devastating effects of this toxin. Because of its rapid binding to in vivo receptors, this toxin is difficult to detect in serum. This rapid binding also constitutes a major challenge for the development of effective therapeutic reagents that can neutralize the effects of the toxin in vivo. We have developed a highly sensitive capture enzyme-linked immunosorbent assay that detects SEB in body fluids at very low levels. With this assay, the peak levels of SEB in serum and renal clearance can be measured in mice. After either oral ingestion or nasal inhalation of SEB by mice, this assay documents the transcytosis of SEB across the mucosal membranes into serum within 2 h. Furthermore, this assay was used to compare the SEB levels in different murine models for SEB-induced lethal shock and demonstrated that the coadministration of toxin-enhancing chemicals, such as d-galactosamine and lipopolysaccharide, can alter the peak serum SEB levels. Hence, this assay is a potentially useful tool for the study of the pharmacokinetics of SEB and the effects of potential therapeutic reagents on serum SEB levels.

scholarly journals Effective Treatment of Staphylococcal Enterotoxin B Aerosol Intoxication in Rhesus Macaques by Using Two Parenterally Administered High-Affinity Monoclonal Antibodies

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Daniel Verreault ◽  
Jane Ennis ◽  
Kevin Whaley ◽  
Stephanie Z. Killeen ◽  
Hatice Karauzum ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primate ◽  
Rhesus Macaques ◽  
Clinical Signs ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Primate Model ◽  
Content Type ◽  
Enterotoxin B

ABSTRACTStaphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface ofStaphylococcus aureusthat is the source for multiple pathologies in humans. When purified and concentrated in aerosol form, SEB can cause an acute and often fatal intoxication and thus is considered a biological threat agent. There are currently no vaccines or treatments approved for human use. Studies with rodent models of SEB intoxication show that antibody therapy may be a promising treatment strategy; however, many have used antibodies only prophylactically or well before any clinical signs of intoxication are apparent. We assessed and compared the protective efficacies of two monoclonal antibodies, Ig121 and c19F1, when administered after aerosol exposure in a uniformly lethal nonhuman primate model of SEB intoxication. Rhesus macaques were challenged using small-particle aerosols of SEB and then were infused intravenously with a single dose of either Ig121 or c19F1 (10 mg/kg of body weight) at either 0.5, 2, or 4 h postexposure. Onset of clinical signs and hematological and cytokine response in untreated controls confirmed the acute onset and potency of the toxin used in the challenge. All animals administered either Ig121 or c19F1 survived SEB challenge, whereas the untreated controls succumbed to SEB intoxication 30 to 48 h postexposure. These results represent the successful therapeuticin vivoprotection by two investigational drugs against SEB in a severe nonhuman primate disease model and punctuate the therapeutic value of monoclonal antibodies when faced with treatment options for SEB-induced toxicity in a postexposure setting.

scholarly journals Electrical activity in rat cortico-limbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B

2010 ◽  
Vol 278 (1713) ◽  
pp. 1864-1872 ◽  
Author(s):  
Raphael Doenlen ◽  
Ute Krügel ◽  
Timo Wirth ◽  
Carsten Riether ◽  
Andrea Engler ◽  
...  
Keyword(s):  
T Cell ◽  
Electrical Activity ◽  
Neural Activity ◽  
Insular Cortex ◽  
Repeated Administration ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Adult Rats ◽  
Enterotoxin B

Immune-to-brain communication is essential for an individual to aptly respond to challenging internal and external environments. However, the specificity by which the central nervous system detects or ‘senses’ peripheral immune challenges is still poorly understood. In contrast to post-mortem c-Fos mapping, we recorded neural activity in vivo in two specific cortico-limbic regions relevant for processing visceral inputs and associating it with other sensory signalling, the amygdala (Am) and the insular cortex (IC). Adult rats were implanted with deep-brain monopolar electrodes and electrical activity was monitored unilaterally before and after administration of two different immunogens, the T-cell-independent antigen lipopolysaccharide (LPS) or the T-cell-dependent antigen staphylococcal enterotoxin B (SEB). In addition, the neural activity of the same individuals was analysed after single as well as repeated antigen administration, the latter inducing attenuation of the immune response. Body temperature and circulating cytokine levels confirmed the biological activity of the antigens and the success of immunization and desensitization protocols. More importantly, the present data demonstrate that neural activity of the Am and IC is not only specific for the type of immune challenge (LPS versus SEB) but seems to be also sensitive to the different immune state (naive versus desensitization). This indicates that the forebrain expresses specific patterns of electrical activity related to the type of peripheral immune activation as well as to the intensity of the stimulation, substantiating associative learning paradigms employing antigens as unconditioned stimuli. Overall, our data support the view of an intensive immune-to-brain communication, which may have evolved to achieve the complex energetic balance necessary for mounting effective immunity and improved individual adaptability by cognitive functions.

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