Overexpression of the T-cell receptor V beta 3 in transgenic mice increases mortality during infection by enterotoxin A-producing Staphylococcus aureus.
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 V beta 3 transgenic (TGV beta 3) 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 V beta 3. Within 9 days after inoculation, 85% of the TGV beta mice died, compared with 31% of their non-TG littermates (P < 0.01). The high mortality of TGV beta 3 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 1 beta (IL-1 beta) mRNA and sparsely expressed tumor necrosis factor alpha (TNF-alpha), 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 TGV beta 3 mice, in contrast to non-TG mice. Impressively, significantly higher expression of TNF-beta mRNA in TGV beta 3 mice was noted throughout the course of infection than in non-TG littermates. These findings suggest that overproduction of TNF-beta and gamma interferon, the Th1 cytokines, may play a crucial role in the pathogenesis of septicemia caused by enterotoxin-secreting staphylococci.
Zhao
Y X
YX
Department of Clinical Immunology, University of Göteborg, Sweden.
Abdelnour
A
A
Kalland
T
T
Tarkowski
A
A
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004768:Enterotoxins / Q000633:toxicity*; D015870:Gene Expression; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000472:pathogenicity*
D016207:Cytokines; D004768:Enterotoxins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C026066:enterotoxin A, Staphylococcal