Human PSG1a induces, directly and through the induction of Th17 cells, the proangiogenic factors IL-6 and VEGF in JEG-3 choriocarcinoma cell line

MARTINEZ, FERNANDO; KNUBEL, C; MOTRAN, CLAUDIA CRISTINA

Vina del Mar. Chile

Congreso; 9th Latin American Congress of Immunology. XII Chilean Society of Immunology. LVII Argentinean Society of Immunology Satellite Scientific Meeting; 2009

ALAI

Indoleamine 2,3-dioxigenase (IDO) is essential for the control of T. cruzi amastigote growth in macrophages.   Carolina P. Knubel, Fernando F. Martinez, Ricardo Fretes and Claudia C Motran*. Clinical Biochemical Department. CIBICI-CONICET. Chemical Sciences Faculty. National University of Cordoba. *cmotran@fcq.unc.edu.ar   IDO, an intracellular enzyme, catalyses the initial step of tryptophan (Trp) catabolism leading to the production of immunomodulatory catabolites, collectively called “kynurenines”. Depletion of Trp and the production of “kynurenines” are responsible for the activities observed after IDO induction including inhibition of intracellular pathogens replication and lymphocyte proliferation and Treg induction.  We demonstrated that in vivo IDO blockade impairs the resistance of mice to T. cruzi infection.  To study the effect of IDO activity on the regulation of intracellular T cruzi growth, we used murine bone marrow derived Mo. IDO blockade by 1-MT resulted in a strong induction of parasite growth. Trp supplementation promoted T. cruzi replication but to levels that were lower than those observed in 1-MT-treated cultures. Moreover, the supplementation with the kynurenine (Kyn) downstream metabolite 3-HK but not Kyn, 3-HAA or QA inhibited the intracellular parasite replication. However, 3-HK, 3-HAA and QA were all able to reduce the intracellular parasite replication in cultures with 1-MT.  We, also observed that 3-HK acted by a direct trypanocidal activity rather than by inducing Mo activation.  These findings indicate the essential requirement of IDO activity through Trp catabolites for the control of T. cruzi replication in Mo.