Streptococcal erythrogenic toxins induce tryptophan degradation in human peripheral blood mononuclear cells

Background: In various cells including monocytes the cytokine interferon-gamma as well as lipopolysaccharide induce indoleamine 2,3-dioxygenase which degrades tryptophan to form L-kynurenine. We addressed the question of whether the exposure of human peripheral mononuclear cells to superantigens derived from streptococci is associated with tryptophan degradation in vitro. Methods: Peripheral blood mononuclear cells were exposed to streptococcal erythrogenic toxins A and B and a streptococcal-derived mitogen named BX. In addition, the myelomonocytic cell line THP-1 was treated with these toxin preparations. Results: In peripheral blood mononuclear cells all three toxins induced tryptophan degradation. In parallel, production of interferon-gamma was found, and the tryptophan degradation could be blocked by antihuman interferon-gamma antibodies. Tryptophan degradation was not induced when the human myelocytoma cell line THP-1 was stimulated with these toxins, but there was a costimulatoty effect to interferon-gamma. Conclusions: In peripheral blood mononuclear cell culture streptococcal erythrogenic toxins are able to stimulate tryptophan degradation in humans via the induction of interferon-gamma production. There seems to be no direct effect on myelomonocytic THP-1 cells. Because some of the degradation products of tryptophan, such as quinolinic acid and kynurenic acid, are toxic, superantigen-driven degradation of tryptophan may play a role for example in the development of the toxic-shock-like syndrome associated with severe group A streptococcal infections.