Tryptophan metabolism and immune alterations in pregnant Hispanic women with chronic Toxoplasma gondii infection

Problem: Pregnancy markedly modifies women's metabolism and immune functions. We hypothesized that pregnancy might alter the immune and metabolic responses to chronic Toxoplasma gondii infection in pregnancy. Method of study: A population of 690 pregnant Hispanic women were screened for antibodies to T. gondii and 158 womenwere positive (23% positivity) with 83% showing high avidity indices. These seropositive women were followed through their pregnancies with four data collection time points and a postpartum collection at two clinics in Tampa, Florida. AT. gondii seronegative group (N= 128) was randomly selected to serve as a control group andmeasured along pregnancy in the sameway. Serum levels of tryptophan, kynurenine, and their ratio, phenylalanine, tyrosine and their ratio, neopterin, and nitrite were measured through pregnancy and the postpartum. A plasma cytokine panel (IFN-gamma, TNF alpha, IL-2, IL-10, IL-12, IL-6, IL-17) was analyzed in parallel. Results: Themajor findings suggest that indoleamine 2,3-dioxygenase (IDO-1) was less activated in T. gondii seropositive pregnantHispanicwomenwith chronic infection. Evidence for IDO-1 suppression was that tryptophan catabolism was less pronounced and there were lower levels of multiple inflammatory cytokines including IFN-., which is the major inducer of IDO-1, and higher nitrite concentration, a surrogate marker for nitric oxide, an inhibitor of IDO. Conclusions: Latent T. gondii infection was associated with higher plasma tryptophan levels, and lower inflammatory cytokines across pregnancy, suggesting suppression of the IDO-1 enzyme, and possible T cell exhaustion during pregnancy.