Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D

Abstract

Mice (BALB/cJ, C3H/HeN, and C3HIHeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C311/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an important cofactor in intoxication. In a time course study of the illness, prominent pathological changes characterized by blood congestion and thickening of alveolar septa were seen in the lung, while blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen, congestion, inflammation, and lymphoid cell depletion were the major reactions. The pathological features of the mice had many similarities to those of rhesus monkeys intoxicated with intravenous SEB. The actinomycin D-primed C3HI1eJ mice are thus an ideal mouse model for studying SEB toxicosis and toxic shock * Corresponding author.

Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire

“…Upon considering the many Gramnegative bacteria that compose the intestinal flora, and increased numbers found in the vaginal flora of TSS patients, odds of this synergy naturally occurring are really quite high [164,165]. 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].…”

“…Mice are often used for obtaining a basic understanding of how toxins (and other biologically-active substances) interact in vivo, which includes the immunological mechanisms that promote superantigen-mediated shock [148][149][150][151][152][153][154][155][156]. Although these animals curiously lack an emetic response, they are cost-effectively ideal for in vivo screening of potential vaccines and therapeutics.…”

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

“…Primates respond to ingestion of SEB by vomiting, and intravenous or inhaled SEB can be fatal to them (5,41). Mice do not have a vomiting mechanism (5) and are insensitive to the lethal effects of injected SEB (53) unless they are pretreated in some way, such as with actinomycin D (14) or D-galactosamine (42). Therefore, the present study was undertaken to test whether CsA would protect monkeys against SEB intoxication, and to study the mechanism of protection.…”

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

“…Staphylococcus aureus causes many diseases in humans (6), and superantigens like the staphylococcal enterotoxins (SEs) plus toxic shock syndrome toxin 1 (TSST-1) are considered important virulence factors that induce immunosuppression in a host, thus providing a distinctly advantageous scenario for a pathogen (11,25). Current in vivo investigations with the SEs and TSST-1 have vigorously concentrated on murine models (9,20,28,32). Relative to the monkey emetic (36) or rabbit (7) models, mice afford an inexpensive alternative for studying (i) the in vivo effects of the SEs and TSST-1, (ii) neutralizing antibodies and therapeutics used against the SEs and TSST-1, and (iii) recombinantly attenuated SEs and TSST-1 used as vaccine candidates (1,32,33,39,40).…”