Malaria parasite induces tryptophan-related immune suppression in mice

Plasmodium spp. cause the worst parasitic diseases in humans and evade host immunity in complicated ways. Activated catabolism of tryptophan in dendritic cells is thought to suppress immunity, which is mediated by an inducible rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3 dioxygenase (IDO), via both tryptophan depletion and production of toxic metabolites. In various infections, including malaria, IDO is known to be activated but its biological significance is unclear; therefore, we investigated whether malaria parasites induce IDO to suppress host immune responses. We found that enzymatic activity of IDO was elevated systematically in our mouse malaria model, and was abolished by in vivo IDO inhibition with 1-methyl tryptophan. Experimental infection with Plasmodium yoelii showed that IDO inhibition slightly suppressed parasite density in association with enhanced proliferation and IFN-γ production by CD4⁺ T cells in response to malaria parasites. Our observations suggest that induction of IDO is one of the immune mechanisms of malaria parasites.