Overexpression of the T-cell receptor Vβ3 in transgenic mice increases mortality during infection by enterotoxin A-producing Staphylococcus aureus

Abstract

We have previously demonstrated that staphylococcal enterotoxins contribute to arthritis and mortality during staphylococcal infection. To further explore the mechanism by which bacterial superantigens contribute to the pathogenesis of Staphylococcus aureus septicemia, T-cell receptor Vβ3 transgenic (TGVβ3) mice and nontransgenic (non-TG) littermates were inoculated intravenously with S. aureus AB-1, which produces large amounts of staphylococcal enterotoxin A, which specifically reacts with T-cell receptor Vβ3. Within 9 days after inoculation, 85% of the TGVβ3 mice died, compared with 31% of their non-TG littermates (P < 0.01). The high mortality of TGVβ3 mice was accompanied by elevated bacterial burdens in the blood, spleen, and kidneys. The in vivo kinetics of cytokine mRNA expression was studied by an in situ hybridization technique. Staphylococcal infection gave rise to increased expression of interleukin 1β (IL-1β) mRNA and sparsely expressed tumor necrosis factor alpha (TNF-α), IL-4, and IL-10 mRNAs in both groups. Gamma interferon mRNA expression increased on day 3 and was maintained at a detectable level in the late phase of infection in TGVβ3 mice, in contrast to non-TG mice. Impressively, significantly higher expression of TNF-β mRNA in TGVβ3 mice was noted throughout the course of infection than in non-TG littermates. These findings suggest that overproduction of TNF-β and gamma interferon, the Th1 cytokines, may play a crucial role in the pathogenesis of septicemia caused by enterotoxin-secreting staphylococci.