Colonic bacterial superantigens evoke an inflammatory response and exaggerate disease in mice recovering from colitis

There is renewed interest in commensal bacteria as triggers of idiopathic disease, a concept that is prominent in inflammatory bowel disease (IBD). Here the effect of intracolonic instillation of Staphylococcus aureus enterotoxin B (SEB), a model superantigen (SAgs: potent T-cell stimuli), into mice was examined.

Mice (Balb/c, severe combined immunodeficient [SCID], V beta 8(+) ovalbumin transgenic [OVA-Tg], interleukin 10 [IL-10] knockout [KO]) received a single intrarectal (IR) dose of SAg and colonic form (histology, myeloperoxidase [MPO] activity) and function (ion transport) were assessed 12-72 hours later. In subsequent studies the potential for SEB to reactivate disease in mice recovering from dextran sodium sulfate (DSS)-induced colitis (5 days at 4% [wt/vol] followed by 14 days normal water) was examined.

SEB-treated Balb/c mice displayed a time- and dose-dependent colonic inflammation (increased MPO, histologic damage score, and macrophage number). Similar events occurred in response to other SAgs, namely S. aureus enterotoxin A (SEA) and Yersinia pseudotuberculosis mitogen. Ion transport, the driving force for water movement, was unaffected by SEB treatment. SCID mice developed no inflammation after IR SEB delivery, whereas OVA Tg mice displayed enhanced responsiveness. Although SEB treatment of IL-10 KO mice did elicit a response, the inflammation was transitory and did not hasten the spontaneous colitis seen in these mice. Finally, mice recovering from DSS-induced colitis showed a worsening of the disease when challenged with SEB; IR SEB evoked significant increases in MPO, macrophage infiltration, T-cell activation (i.e., CD25 expression), and perturbed epithelial ion transport.

Lumen-derived bacterial SAgs can elicit a local inflammation and aggravate enteric inflammatory disorders in which they were not the causative agent.