Mucosal tolerance to a bacterial superantigen indicates a novel pathway to prevent toxic shock.
Enterotoxins with superantigenic properties secreted during systemic Staphylococcus aureus infection are responsible for toxic shock. We show that intranasal administration of staphylococcal enterotoxin A (SEA), but not a recombinant SEA lacking superantigenic activity, protected mice against lethal systemic SEA challenge. Protection was superantigen specific since intranasal exposure to SEA would not protect against death caused by subsequent toxic shock syndrome toxin 1 systemic challenge. Protection was neither due to selective depletion of SEA-specific T-cell receptor Vbeta families nor due to production of neutralizing anti-SEA antibodies. Importantly, the production of interleukin 10 (IL-10) induced by "tolerization" (that is, by the induction of immunological tolerance) contributed to the observed protection against lethal superantigen-triggered disease. In support of this notion we found that (i) significantly increased levels of IL-10 in sera of "tolerized" animals (that is, animals rendered tolerant) and (ii) IL-10(-/-) mice could not be tolerized by mucosal SEA administration. Altogether, this is the first study to show that mucosal tolerance to a superantigen is readily triggered by means of immunodeviation.
Collins
L Vincent
LV
Department of Rheumatology, University of Göteborg, Göteborg, Sweden. vincent.collins@rheuma.gu.se
Eriksson
Kristina
K
Ulrich
Robert G
RG
Tarkowski
Andrej
A
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D016753:Interleukin-10 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012772:Shock, Septic / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D004768:Enterotoxins; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal