Changes in Murine Jejunal Morphology Evoked by the Bacterial SuperantigenStaphylococcus aureusEnterotoxin B Are Mediated by CD4⁺T Cells

Abstract

Bacterial superantigens (SAgs) are potent T-cell stimuli that have been implicated in the pathophysiology of autoimmune and inflammatory disease. We used Staphylococcus aureus enterotoxin B (SEB) as a model SAg to assess the effects of SAg exposure on gut form and cellularity. BALB/c, SCID (lacking T cells) and T-cell-reconstituted SCID mice were treated with SEB (5 or 100 μg intraperitoneally), and segments of the mid-jejunum were removed 4, 12, or 48 h later and processed for histochemical or immunocytochemical analysis of gut morphology and major histocompatibility complex class II (MHC II) expression and the enumeration of CD3+ T cells and goblet cells. Control mice received saline only. SEB treatment of BALB/c mice caused a time- and dose-dependent enteropathy that was characterized by reduced villus height, increased crypt depth, and a significant increase in MHC II expression. An increase in the number of CD3+ T cells was observed 48 h after exposure to 100 μg of SEB. Enteric structural alterations were not apparent in SEB-treated SCID mice compared to saline-treated SCID mice. In contrast, SEB challenge of SCID mice reconstituted with a mixed lymphocyte population or purified murine CD4+ T cells resulted in enteric histopathological changes reminiscent of those observed in SEB-treated BALB/c mice. These findings implicate CD4+ T cells in this SEB-induced enteropathy. Our results show that SAg immune activation causes significant changes in jejunal villus-crypt architecture and cellularity that are likely to impact on normal physiological processes. We speculate that the elevated MHC II expression and increased number of T cells could allow for enhanced immune responsiveness to other SAgs or environmental antigens.

Dietary Plasma Protein Affects the Immune Response of Weaned Rats Challenged with S. aureus Superantigen B

“…In the spleen, the cell populations were similar to those described for adult Lewis rats (44) and no effects of SEB were observed, supporting the view that SEB affects mainly the physiology of the intestinal epithelium (15). Because the systemic variables measured in the present study were not modified by SEB administration or diet supplementation, we conclude that the major effects of SEB and diets take place at the intestinal level, in agreement with previous observations (12,22).…”

“…The i.p. route is widely used in models of intestinal inflammation (15,22) because the oral route has the disadvantage that the amount of SEB reaching the mucosa is variable because it can be hydrolyzed by enteric enzymes, thus requiring coadministration of trypsin inhibitors (23). We chose rats at the weaning period because the mucosal immune system is still immature and therefore more susceptible to infection.…”

Evolving superantigens of Staphylococcus aureus

“…Acute e¡ects in humans range from self-limiting gastrointestinal distress to life-threatening toxic-shock syndrome (TSS). Enteric pathology is T-cell-dependent [17] and presumably results from a cytokine toxicity that is similar to TSS but localized. In addition, bacterial SAgs activate experimental autoimmune diseases [18].…”

Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation

“…By contrast, severe and often fatal inflammatory intestinal disease may occur if enteric exposure to toxin‐producing staphylococci is prolonged or host defenses impaired 2. Chronic staphylococcal enterocolitis has been established in animals using both whole organisms and enterotoxins 3–5. Severe inflammation was induced in human fetal small bowel explants when cultured in the presence of SEB 6.…”