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Malaria parasite induces tryptophan-related immune suppression in mice

Published online by Cambridge University Press:  22 February 2007

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: [email protected]

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.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Adikari, S. B., Lian, H., Link, H., Huang, Y. M. and Xiao, B. G. (1988). Interferon-gamma-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis. Journal of Interferon Research 8, 691702.Google Scholar
Billker, O., Lindo, V., Panico, M., Etienne, A. E., Paxton, T., Dell, A., Rogers, M., Sinden, R. E. and Morris, H. R. (1998). Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature, London 392, 289292.CrossRefGoogle ScholarPubMed
Cady, S. G. and Sono, M. (1991). 1Methyl-DL tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan)are competitive inhibitors for indoleamine 2,3 dioxygenase. Archives of Biochemistry and Biophysics 291, 326333.CrossRefGoogle Scholar
Coban, C., Ishii, K. J., Kawai, T., Hemmi, H., Sato, S., Uematsu, S., Yamamoto, M., Takeuchi, O., Itagaki, S., Kumar, N., Horii, T. and Akira, S. (2005). Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. Journal of Experimental Medicine 201, 1925.CrossRefGoogle ScholarPubMed
Fujioka, H., Kato, N., Fujita, M., Fujimura, K. and Nishiyama, Y. (1990). Activities of new acridone alkaloid derivatives against Plasmodium yoelii in vitro. Arzneimittel Forschung 40, 10261029.Google ScholarPubMed
Gurtner, G. J., Newberry, R. D., Schloemann, S. R., McDonald, K. G. and Stenson, W. F. (2003). Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice. Gastroenterology 125, 17621773.CrossRefGoogle ScholarPubMed
Hansen, A. M., Driussi, C., Turner, V., Takikawa, O. and Hunt, N. H. (2000). Tissue distribution of indoleamine 2,3-dioxygenase in normal and malaria-infected tissue. Redox Report: Communications in Free Radical Research 5, 112115.CrossRefGoogle Scholar
Helleberg, M., Goka, B. Q., Akanmori, B. D., Obeng-Adjei, G., Rodriquies, O. and Kurtzhals, J. A. L. (2005). Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia. Malaria Journal 4, 56.CrossRefGoogle ScholarPubMed
Hisaeda, H., Maekawa, Y., Iwakawa, D., Okada, H., Himeno, K., Kishihara, K., Tsukumo, S. and Yasutomo, K. (2004). Escape of malaria parasites from host immunity requires CD4+CD25+ regulatory T cells. Nature Medicine 10, 2930.CrossRefGoogle ScholarPubMed
Hisaeda, H., Yasutomo, K. and Himeno, K. (2005). Malaria: immune evasion by parasites. International Journal of Biochemistry and Cell Biology 37, 700706.CrossRefGoogle ScholarPubMed
Ing, R., Segura, M., Thawani, N., Tam, M. and Stevenson, M. M. (2006). Interaction of mouse dendritic cells and malaria-infected erythrocytes: uptake, maturation, and antigen presentation. Journal of Immunology 176, 441450.CrossRefGoogle ScholarPubMed
Mellor, A. L. and Munn, D. H. (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nature Reviews Immunology 4, 762774.CrossRefGoogle ScholarPubMed
Millington, O. R., Di Lorenzo, C., Phillips, R. S., Garside, P. and Brewer, J. M. (2006). Suppression of adaptive immunity to heterologous antigens during plasmodium infection through hemozoin-induced failure of dendritic cell function. Journal of Biology (Online) 5, 5.CrossRefGoogle ScholarPubMed
Mitchell, A. J., Hansen, A. M., Hee, L., Ball, H. J., Potter, S. M., Walker, J. C. and Hunt, N. H. (2005) Early cytokine production is associated with protection from murine cerebral malaria. Infection and Immunity 73, 56455653.CrossRefGoogle ScholarPubMed
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I., Conway, S. J., Marshall, B., Brown, C. and Mellor, A. L. (1998). Prevention of allogeneic faetal rejection by tryptophan catabolism. Science 281, 11911193.CrossRefGoogle Scholar
Munn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., Messina, J. L., Chandler, P., Koni, P. A. and Mellor, A. L. (2004). Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumour-draining lymph nodes. Journal of Clinical Investigation 114, 280290.CrossRefGoogle Scholar
Ocana-Mongner, C., Mota, M. M. and Rodriguez, A. (2003). Malaria blood stage suppression of liver stage imunity by dendritic cells. Journal of Experimental Medicine 197, 143151.CrossRefGoogle Scholar
Pawlak, D., Tankiewicz, A., Mysliwiec, P. and Buczko, W. (2002). Tryptophan metabolism via the kynurenine pathway in experimental chronic renal failure. Nephron 90, 328335.CrossRefGoogle ScholarPubMed
Pichyangkul, S., Yongvanitchit, K., Kum-arb, U., Hemmi, H., Akira, S., Krieg, A. M., Heppner, D. G., Stewart, V. A., Hasegawa, H., Looareesuwan, S., Shanks, G. D. and Miller, R. S. (2004). Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway. Journal of Immunology 172, 49264933.CrossRefGoogle ScholarPubMed
Rescigno, M. and Borrow, P. (2001). The host-pathogen interaction: new themes from dendritic cell biology. Cell 106, 267270.CrossRefGoogle ScholarPubMed
Sakurai, K., Zou, J. P., Tschetter, R., Ward, J. M. and Shearer, G. M. (2002). Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 129, 186196.CrossRefGoogle ScholarPubMed
Sanni, L. A., Thomas, S. R., Tattam, B. N., Moore, D. E., Chaudhri, G., Stocker, R. and Hunt, N. H. (1998). Dramatic change in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. American Journal of Pathology 152, 611619.Google ScholarPubMed
Shear, H. L., Srinivasan, R., Nolan, T. and Ng, C. (1989). Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts. Journal of Immunology 143, 20382044.CrossRefGoogle ScholarPubMed
Takikawa, O., Yoshida, R., Kido, R. and Hayaishi, O. (1986). Tryptophan degradation in mice initiated by indoleamine 2,3 dioxygenase. Journal of Biological Chemistry 261, 36483653.CrossRefGoogle ScholarPubMed
Tosta, C. E., Sedegah, M., Henderson, D. C. and Wedderburn, N. (1980). Plasmodium yoelii and Plasmodium berghei: isolation of infected erythrocytes from blood by colloidal silica gradient centrifugation. Experimental Parasitology 50, 715.CrossRefGoogle ScholarPubMed
Urban, B. C., Ferguson, D. J. P., Pain, A., Willcox, N., Plebanski, M., Austyn, J. M. and Roberts, D. J. (1999). Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cell. Nature, London 400, 7377.CrossRefGoogle Scholar
Uyttenhove, C., Pilotte, L., Theate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T. and van den Eynde, B. J. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3 dioxygenase. Nature Medicine 9, 12691274.CrossRefGoogle ScholarPubMed
Xu, H., Wipasa, J., Yan, H., Zeng, M., Makobongo, M. O., Finkelman, F. D., Kelso, A. and Good, M. F. (2002). The mechanism and significance of deletion of parasite-specific CD4+ T cells in malaria infection. Journal of Experimental Medicine 195, 881892.CrossRefGoogle ScholarPubMed