Helicobacter pylori-induced indoleamine 2,3-dioxygenase activity in vivo is regulated by TGFB1 and CTLA4 polymorphisms.
The chronic gastric infection caused by Helicobacter pylori is known to be associated with several, probably interrelated, immunomodulatory effects, such as protection from atopic diseases, induction of CD4+ CD25+ T regulatory (T(reg)) cells and increase in indoleamine-pyrrole 2,3-dioxygenase (IDO) -dependent suppressive mechanisms. As these mechanisms, as well as the strength of the infection, are very probably genetically controlled, we selected candidate genes (TGFB1, CTLA4) known to be involved in the activation of T(reg) cells. We examined the association of their polymorphisms (TGFB1 C-509T, CTLA4 A+49G) with blood IDO activity in H. pylori seropositive individuals. Genotypes were determined from 391 healthy adults. H. pylori infection was verified by detecting H. pylori IgG antibodies in sera. Concentrations of tryptophan (trp) and kynurenine (kyn), the main metabolite, were determined by reverse-phase high-performance liquid chromatography, and kyn/trp ratio was used as an indicator of IDO activity. The activity was higher in H. pylori seropositive individuals, but this increase was only detected in individuals with CTLA4+49 AA genotype or in carriers of TGFB1-509 allele T. This suggests that H. pylori induced IDO activity is regulated by TGFB1 and CTLA4, and that IDO is a mediator of the T cell suppressive effects of these genes.
Raitala
Annika
A
University of Tampere Medical School, Tampere, Finland. annika.raitala@uta.fi
Karjalainen
Jussi
J
Oja
Simo S
SS
Kosunen
Timo U
TU
Hurme
Mikko
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014364:Tryptophan / Q000097:blood
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007074:Immunoglobulin G; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053773:Transforming Growth Factor beta1; D007737:Kynurenine; D014364:Tryptophan