Treatment of mice with staphylococcal enterotoxin B enhances resolution of an induced Escherichia coli urinary tract infection and stimulates production of proinflammatory cytokines

Abstract

Staphylococcal enterotoxin B (SEB) is a superantigen that causes mass proliferation of murine Vbeta8+ T cells via major histocompatibility complex (MHC) class II molecules and leads to their apoptosis or anergy. SEB also stimulates other MHC class II-bearing cells to proliferate and secrete cytokines, some of which might enhance early host defenses against urinary tract infections (UTIs). We investigated the effect of SEB administration on the course of an induced Escherichia coli UTI in mice. Treatment with SEB 3 or 7 days before the infection had no effect on UTI resolution. However, when SEB was administered at the time of infection, bacterial colonization in the bladders was reduced at time points between 6 h and 3 days. This reduction was not due to a physiological effect, such as increased urinary glycosaminoglycans, or altered pH, nor was SEB bactericidal for the inoculum. Cytokine production in the spleens and bladders of SEB-treated and/or infected mice was evaluated by reverse transcription-PCR. SEB treatment resulted in increased levels of interleukin-2 (IL-2), IL-4, IL-6, and IL-10 mRNAs in the spleen and IL-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha transcripts in the bladder. Also, liver cells from SEB-treated mice expressed IL-6 mRNA, which induces the production of acute-phase proteins. These data indicate that SEB treatment in vivo leads to enhanced UTI resolution through a mechanism that may include direct stimulation of effector cells in the bladder, the action of cytokines induced in the spleen, or cytokine-mediated induction of acute-phase proteins.

FIG. 1

SEB injection given concurrently with UTI induction accelerates infection resolution. Mice were given 50 μg of SEB i.p. (•) at the time of intravesical inoculation with 10⁸ CFU of strain 1677. Control animals (○) received the bacterial inoculum only. A total of 8 to 24 mice were assayed per time point when repeat experiments were pooled.

FIG. 2

Cytokine mRNA expression levels in spleen cells following SEB treatment in vivo and/or induced UTI. Lane 1, infection only; lane 2, SEB plus infection; lane 3, SEB only; lane 4, untreated control. The upper band in each lane is the β-actin transcript. Results from the 6-, 12-, and 24-h time points did not significantly differ; therefore, a representative gel from each group is shown.

FIG. 3

Cytokine mRNA expression levels in bladder cells following SEB treatment in vivo and/or induced UTI. Lane 1, infection only; lane 2, SEB plus infection; lane 3, SEB only; lane 4, untreated control. The upper band in each lane is the β-actin transcript. Results from the 6-, 12-, and 24-h time points did not significantly differ; therefore, a representative gel from each group is shown.

FIG. 4

IL-6 mRNA expression levels in liver cells 12 h after SEB treatment in vivo. Lanes 1 to 4, RT-PCR products from four individual mice receiving 50 μg of SEB i.p.; lanes 5 to 8, RT-PCR products from four untreated control mice. The upper band is the β-actin transcript.