Murine Lethal Toxic Shock Caused by Intranasal Administration of Staphylococcal Enterotoxin B

Abstract

Currently available murine staphylococcal enterotoxin B (SEB) shock models require pretreatment with various agents to increase mouse sensitivity to SEB. This study was performed to show that C3H/HeJ mice are highly susceptible to intranasal SEB inoculation, which caused toxic shock without using pretreatment agents. For this purpose, mice were injected intranasally with different doses of SEB and observed for up to 1 month. The median lethal dose of SEB was determined using the probit procedure. Tissue samples were taken at different time points for histopathological examination. The LD(50) was found at 1.6 microg/g (95% fiducial limit (f.l.) 0.7 to 2.2), the LD(80) at 2.7 microg/g (95% f.l. 1.9 to 4.0) and the LD(90) at 3.6 microg/g (95% f.l. 2.7 to 6.4). Histopathologic examination revealed pulmonary edema and bronchopneumonia. Mucosal-associated lymphoid tissue first became activated, followed by increasing lymphocyte apoptosis and depletion. In the liver there were intralobular and portal inflammatory foci with increasing lymphocyte apoptosis and degenerative necrosis. The splenic white pulp was characterized by early activation and subsequent depletion of lymphoid follicle germinal centers. The thymus initially was activated, followed by increasing apoptosis and migration of lymphoid cells from the cortex to the medulla. The pathological features detected in the mice were similar to those of rhesus monkeys treated with SEB aerosol challenge.

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

“…These two relatively small SEB challenges trigger intense inflammation in the lung and systemic cytokine release that culminate in death more than 3 days after the initial exposure. Importantly, cytokine release, pathological lesions, and time to lethality in C3H/HeJ mice resemble findings in primate studies [30], [33], [34], [35] and clinical staphylococcal toxic shock syndrome in patients [1]. Furthermore, respiratory system challenge with the induction of a pulmonary inflammatory response simulates the manner in which SEB would be used as a bioweapon [15].…”

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

“…taphylococcal enterotoxin B (SEB), a superantigen produced by Staphylococcus aureus, has deleterious effects in humans, such as food poisoning (1) and toxic shock (2). Because it can be easily aerosolized, SEB is classified as a category B agent by the Centers for Disease Control and Prevention (3).…”

Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock

“…A high IN dose of SEB was reported to be lethal in C3H/HeJ, a TLR4-defective mouse strain, but the mechanism of intoxication was unclear [108]. A recent study revealed that this dose of SEB was ineffective in mediating SEB-induced shock, although two low doses of SEB, at least one dose must be delivered by IN, were lethal [79].…”