title: CNS activational responses to staphylococcal enterotoxin B: T-lymphocyte-dependent immune challenge effects on stress-related circuitry.
abstract: Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that engages the immune system in a T-lymphocyte-dependent manner and induces a cytokine profile distinct from that elicited by the better-studied bacterial pathogen analog, lipopolysaccharide (LPS). Because of reports of SEB recruiting central nervous system (CNS) host defense mechanisms via pathways in common with LPS, we sought to further characterize central systems impacted by this agent. Rats were treated with SEB at doses of 50-5,000 mug/kg, and killed 0.5-6 hours thereafter. SEB injection produced a discrete pattern of Fos induction in brain that peaked at 2-3 hours postinjection and whose strength was dose-related. Induced Fos expression was predominantly subcortical and focused in a set of interconnected central autonomic structures, including aspects of the bed n. of the stria terminalis, central amygdala and lateral parabrachial nuclei; functionally related (and LPS-responsive) cell groups in the n. solitary tract, ventrolateral medulla, and paraventricular hypothalamic n. (PVH) were, by contrast, weakly responsive. SEB also activated cell groups in the limbic forebrain (lateral septal n, medial prefrontal cortex) and hypothalamic GABAergic neurons, which could account for its failure to elicit reliable increases in Fos-ir or corticotropin-releasing factor (CRF) mRNA in the PVH. SEB nevertheless did provoke reliable pituitary-adrenal secretory responses. The identification of subsets of central autonomic and limbic forebrain structures that are sensitive to SEB provides a basis for a systems-level understanding of the physiological and behavioral effects attributed to the superantigen. Core SEB-responsive cell groups exclude a medullary-PVH circuit implicated in pituitary-adrenal responses to LPS.
authors.affiliation: Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and The Foundation for Medical Research, La Jolla, California 92037, USA.
authors.forename: Jordi
authors.initials: J
authors.lastname: Serrats
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sawchenko
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007375:Interleukin-1 / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D007375:Interleukin-1; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016761:Oncogene Proteins v-fos; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C031818:enterotoxin B, staphylococcal; D005680:gamma-Aminobutyric Acid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone