INVESTIGADORES
CERVI Laura Alejandra
artículos
Título:
Indoleamine 2,3 Dioxigenase (IDO) is critical for the host resistance against Trypanosoma cruzi.
Autor/es:
KNUBEL, CP,.MARTÍNEZ FF, FRETES RE, DÍAZ LUJAN C, THEUMER M CERVI L AND MOTRÁN CC
Revista:
FASEB JOURNAL
Editorial:
FEDERATION AMER SOC EXP BIOL
Referencias:
Año: 2010
ISSN:
0892-6638
Resumen:
ABSTRACT Indoleamine 2,3-dioxigenase (IDO) is
an inflammatory cytokine-inducible rate-limiting enzyme
of the tryptophan (Trp) catabolism, which is
involved in the inhibition of intracellular pathogen
replication as well as in immunomodulation. Here we
demonstrated the effect of IDO-dependent Trp catabolism
on Trypanosoma cruzi resistance to acute
infection. Infection with T. cruzi resulted in the
systemic activation of IDO. The blocking of IDO
activity in vivo impaired resistance to the infection
and exacerbated the parasite load and infectionassociated
pathology. In addition, IDO activity was
critical to controlling the parasites replication in
macrophages (Mos), despite the high production of
nitric oxide produced by IDO-blocked T. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgIndoleamine 2,3-dioxigenase (IDO) is
an inflammatory cytokine-inducible rate-limiting enzyme
of the tryptophan (Trp) catabolism, which is
involved in the inhibition of intracellular pathogen
replication as well as in immunomodulation. Here we
demonstrated the effect of IDO-dependent Trp catabolism
on Trypanosoma cruzi resistance to acute
infection. Infection with T. cruzi resulted in the
systemic activation of IDO. The blocking of IDO
activity in vivo impaired resistance to the infection
and exacerbated the parasite load and infectionassociated
pathology. In addition, IDO activity was
critical to controlling the parasites replication in
macrophages (Mos), despite the high production of
nitric oxide produced by IDO-blocked T. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgTrypanosoma cruzi resistance to acute
infection. Infection with T. cruzi resulted in the
systemic activation of IDO. The blocking of IDO
activity in vivo impaired resistance to the infection
and exacerbated the parasite load and infectionassociated
pathology. In addition, IDO activity was
critical to controlling the parasites replication in
macrophages (Mos), despite the high production of
nitric oxide produced by IDO-blocked T. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgT. cruzi resulted in the
systemic activation of IDO. The blocking of IDO
activity in vivo impaired resistance to the infection
and exacerbated the parasite load and infectionassociated
pathology. In addition, IDO activity was
critical to controlling the parasites replication in
macrophages (Mos), despite the high production of
nitric oxide produced by IDO-blocked T. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgin vivo impaired resistance to the infection
and exacerbated the parasite load and infectionassociated
pathology. In addition, IDO activity was
critical to controlling the parasites replication in
macrophages (Mos), despite the high production of
nitric oxide produced by IDO-blocked T. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgT. cruziinfected
Mos. Analysis of the mechanisms by which
IDO controls the parasite replication revealed that T.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgT.
cruzi amastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgamastigotes were sensitive to L-kynurenine
downstream metabolites 3-hydroxykynurenine (3-
HK) and 3-hydroxyanthranilic acid, while 3-HK also
affected the trypomastigote stage. Finally, 3-HK
treatment of mice acutely infected with T. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgT. cruzi was
able to control the parasite and to improve the
survival of lethally infected mice. During infection,
IDO played a critical role in host defense against T.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgT.
cruzi; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.org; therefore, the intervention of IDO pathway
could be useful as a novel antitrypanosomatid therapeutic
strategy.Knubel, C. P., Martínez, F. F.,
Fretes, R. E., Lujan, C. D., Theumer, M. G., Cervi, L.,
Motra´n, C. C. Indoleamine 2,3-dioxigenase (IDO) is
critical for host resistance against Trypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.orgTrypanosoma cruzi.
FASEB J. 24, 000 000 (2010). www.fasebj.org24, 000 000 (2010). www.fasebj.org
Key Words: Infection parasites immunomodulation kynurenines parasites immunomodulation kynurenines