Mechanism of Trichinella spiralis-mediated CD4+ T cell functional imbalance via IDO-dependent tryptophan metabolism

Trichinella spiralis (T. spiralis) Infection can upregulate indoleamine 2,3-dioxygenase (IDO) in the host. To assess the relationship between IDO in CD4⁺ T cells (Helper T cells, Th) infected with T. spiralis and the ability of T. spiralis to escape host immune system attack, we investigated the immunomodulatory effects of T. spiralis Infection in mice, focusing on the mechanism by which IDO modulates CD4⁺ T-cell function. The findings of this study revealed that T. spiralis increased IDO levels in mice and upregulated the expression of interleukin 10 (IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor (TNF), but decreased the CD4⁺/CD3⁺ T-cell ratio. This effect was suppressed after 1-methyltryptophan (1-MT) treatment, indicating that it is IDO-dependent. High expression of IDO led to the catabolism of tryptophan via the tryptophan-kynurenine pathway, resulting in the high expression of general control Nonderepressible 2 (GCN2) and the phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). These changes increased the Apoptosis rate of CD4⁺ T cells and reduced their proliferation ability, which was confirmed through in vitro experiments. Additionally, T. spiralis-induced high expression of IDO in mice upregulated Foxp3 expression in CD4⁺CD25⁺ Treg cells, which plays a negative role in immune regulation in mice. Experimental evidence has revealed that mouse CD4⁺ T cells undergo Apoptosis via IDO following T. spiralis Infection, and that weakened proliferation leads to an imbalance in mouse immune function, facilitating the smooth survival of T. spiralis and evasion of host immune attack. These findings provide new directions and insights for studying the immune escape mechanism of T. spiralis and for the prevention and treatment of T. spiralis Infection.

CD4(+) T cells; Immune evasion; Indoleamine 2,3-dioxygenase; Trichinella spiralis; Tryptophan.