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 oftryptophan may play a role for example in the development of the toxic-shock-like syndrome associated with severe group A streptococcal infections.
Murr
C
C
Institute for Medical Chemistry and Biochemistry and Ludwig Boltzmann Institute for AIDS Research, Innsbruck, Austria.
Widner
B
B
Gerlach
D
D
Werner-Felmayer
G
G
Dierich
M P
MP
Wachter
H
H
Fuchs
D
D
D000328:Adult; D001426:Bacterial Proteins; D002478:Cells, Cultured; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007737:Kynurenine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D011749:Pyrogens / Q000494:pharmacology*; D013297:Streptococcus pyogenes / Q000737:chemistry*; D018089:Superantigens / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism*
D001426:Bacterial Proteins; D005098:Exotoxins; D008565:Membrane Proteins; D011749:Pyrogens; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan