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Malaria parasite induces tryptophan-related immune suppression in mice

Published online by Cambridge University Press:  22 February 2007

K. TETSUTANI ,
H. TO ,
M. TORII ,
H. HISAEDA  and
K. HIMENO
K. TETSUTANI*
Affiliation:
Kyushu University Graduate School of Medicine, Department of Parasitology, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-0054, Japan
H. TO
Affiliation:
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Japan
M. TORII
Affiliation:
Department of Molecular Parasitology, Ehime University School of Medicine, Japan
H. HISAEDA
Affiliation:
Kyushu University Graduate School of Medicine, Department of Parasitology, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-0054, Japan
K. HIMENO
Affiliation:
Kyushu University Graduate School of Medicine, Department of Parasitology, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-0054, Japan
*
*Corresponding author: Department of Parasitology, Kyushu University Graduate School of Medicine, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-0054, Japan. Tel: +81 92 642 6117. Fax: +81 92 642 6118. E-mail: tetztani@parasite.med.kyushu-u.ac.jp
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Summary

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.

Keywords

cellular immunityindoleamine 2,3-dioxygenasePlasmodium yoelii
Type
Research Article
Information
Parasitology , Volume 134 , Issue 7 , July 2007 , pp. 923 - 930
Copyright
Copyright © Cambridge University Press 2007

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