Toxic shock syndrome toxin-1 challenges the neuroprotective functions of the choroidal epithelium and induces neurotoxicity.
To probe encephalopathy pathogenesis during toxic shock syndrome (TSS), we investigated the fate of bloodborne TSS toxin-1 (TSST-1) as it moves through the choroid plexus epithelium that forms the main blood-cerebrospinal fluid (CSF) barrier and the effect that TSST-1 has on choroidal barrier properties and on cultured neuronal cell viability. TSST-1 showed a slow, diffusional movement across a cellular model of the blood-CSF barrier but did not compromise the integrity of the barrier. Relevant to the acute symptoms of TSS, a combination of human leukocytes and the toxin induced a decrease in CSF clearance of the pyrogenic prostaglandin E(2) (PGE(2)). The direct effects that TSST-1 had on primary cortical neuron cultures and a neuronal cell line involved elevated caspase 3/7 levels, which correlated with an increase in neuronal cell death. The results of the present study suggest that TSST-1 can affect the brain, by inducing both an intracerebral increase in PGE(2) concentration and caspase-dependent neuronal death, which are possibly relevant to long-term intoxication.
Batisson
Maryline
M
Centre National de Référence des Staphylocoques, INSERM E0230, IFR62, 69372 Lyon cedex 08, France.
Strazielle
Nathalie
N
Hejmadi
Momna
M
Thomas
Damien
D
Ghersi-Egea
Jean Francois
JF
Etienne
Jerome
J
Vandenesch
Francois
F
Lina
Gerard
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001427:Bacterial Toxins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004768:Enterotoxins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000382:microbiology; D051381:Rats; D018089:Superantigens / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D053148:Caspase 3; D053179:Caspase 7; D015232:Dinoprostone