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Parasitología latinoamericana

versión On-line ISSN 0717-7712

Parasitol. latinoam. v.60 n.1-2 Santiago jun. 2005

http://dx.doi.org/10.4067/S0717-77122005000100008 

 

Parasitol Latinoam 60: 54 - 56, 2005 FLAP

ARTÍCULO ORIGINAL

 

Role of interferon - g on the immunosuppression during Toxoplasma gondii infection by Trypanosoma lewisi

 

MISAEL CHINCHILLA*, LILLIANA REYES*, OLGA MARTA GUERRERO* and ALFREDO CASTRO*

* Centro de Investigación en Enfermedades Tropicales, CIET. Departamento de Parasitología, Facultad de Microbiología Universidad de Costa Rica, San José, Costa Rica, América Central.

Dirección para correspondencia


ABSTRACT

On the basis of previous studies on Trypanosoma lewisi immunosuppression model groups of 5 Wistar rats were infected with. T. gondii and T. lewisi according to the following protocol. One group was inoculated i.p. with 106 T. lewisi tripanomastigotes and 4 days later with 107 T. gondii tachyzoites. The second and third groups were infected only with T. lewisi or T. gondii respectively. The fourth group was not infected and served as control. Rats were bled before the infection and then every day for seven days. Serum samples were collected and the levels of IFN-g, IL-2 and TNF-a were measured. The results indicates that the level of IFN-g is very high 24 hour after infection in rats inoculated with T. gondii only, while in those animals infected with both parasites (first group), IFN-g was not detected 24 hours after infections with T. gondii. These data give evidence that a reduction of IFN-g levels is one of the reasons for the immunosuppressive effect induced by T. lewisi, increasing T. gondii multiplication in an animal as the rat, which is remarkable resistant to this parasite.

Key words: Interferon g , immunosuppression, Toxoplasma gondii, Trypanosoma lewisi, white rats natural resistance.

RESUMEN

De acuerdo con estudios anteriores, en donde se ha demostrado el efecto de inmunosupresión producido por Trypanosoma lewisi sobre infecciones con Toxoplasma gondii, grupos de 5 ratas Wistar fueron inoculadas según el siguiente protocolo. Un grupo fue inoculado i.p. con 106 tripomastigotos de T. lewisi y 4 días después con 107 taquizoitos de T. gondii. El segundo y el tercer grupo fueron inoculados sólo con T. gondii o con T. lewisi respectivamente. Un cuarto grupo no fue infectado y sirvió como control. Las ratas fueron sangradas antes de la infección y luego cada día durante 7 días. Los sueron fueron colectados para determinar la presencia de IFN-g, IL-2 y TNF-a .El nivel de IFN-g fue muy alto después de 24 h de infección en las ratas inoculadas únicamente con T. gondii, mientras que en los animales infectados con ambos parásitos (el primer grupo) el IFN-g no fue detectado en el mismo período de infección con T. gondii; IL-2 y TNF-a no fueron detectados. Estos datos son una evidencia preliminar de que en este proceso de inmuno-supresión, existe una reducción en los niveles deIFN-g, inducida por T. lewisi, lo cual es probablemente una de las razones por las que la rata se ve disminuida en su resistencia natural al T. gondii.


INTRODUCTION

Immunosuppression events have been observed after infection with T. brucei1, T. congolense2 and others3, as well as in tripanosomes from rodents4,5. It appears that citokines play an important role in this effect, specially IFN-g, TNFa factor and IL-101,3,6.

We have observed that infection of white rats with T. lewisi makes these animals, which usually are very resistant to T. gondii infections7, as susceptible as mice, either in vivo or in vitro8,9.

According to these observations, the present study was performed in order to determine the role of INF-g, IL-2 and TNFa in the immunosuppression effect exerted by T. lewisi against T. gondii infections.

MATERIAL AND METHODS

Wistar white rats (150-200 g body weigth) obtained from the Animal house of the México Hospital were caged in 4 groups of 5 animals each. Rats of the first group were inoculated i.p. with 106 T. lewisi tripomastigotes and 4 days later the animals were infected i. p. with 107 T. gondii (RH strain) tachyzoites. Rats of the second and third groups were infected with T. lewisi and T. gondii respectively. A fourth group was not infected and served as control. All the animals were bled from the tail vein in serum separation tubes (Becton Dickinson, Vacutainer Systems) before the infection and then every 24 h until for 7 days.

Sera were stored at -200 C and IFN-g, IL-2 and TNFa determinations were done two months later. For the quantitative determination of rat IFN-g, IL-2 and TNF-a concentration in serum, a quantitative ELISA technique (QuantikineR M murine, R & D Systems, Minneapolis, MN, USA) was used.

RESULTS AND DISCUSSION

Figure 1 shows that in the animals infected only with T. gondii, there were high IFN-g levels starting at 24 h after infection. These values diminished to one half after 48 h. On the other hand, in rats previously infected with T. lewisi and then inoculated with T. gondii 4 days later, IFN-g was detected only after 48 h of T. gondii infection. This lymphokine was not found in animals infected only with T. lewisi. Neither IL-2 or TNF-a were detected in the samples.


Figure 1. T. gondii was inoculated on day 4 after T. lewisi infection. 4/0 = T. lewisi infection time/ T. gondii infection time. Determination of INF gamma in rats infected with T. gondii or T. lewisi.

These findings appear to demonstrate that IFN-g plays an important role in this immuno suppressive model caused by T. lewisi. This has also been observed in intracellular parasites10. Regarding to T. gondii, Lüder et al11, made an interesting relation between the role of IFN-g and IL-4 and their effect on the natural resistance of Lewis strain rats to this parasite.

The results showed in Figure 1 indicate an inhibitory effect of IFN-g production apparently due to the previous presence of T. lewisi in T. gondii infected white rats. Since it has been found some immunosuppressive action exerted by T. brucei soluble fragments2, it is possible that protein fractions or excretion products from T. lewisi could be in part responsible, of the immune phenomena observed. To this respect, Ndarathi studies12,13 presented some promissory data. In fact they found that epimastigote extracts probably containing exoantigens of this parasite, caused immunosuppression in infected rats. Since epimastigote forms appear early in the life cycle of this parasite14, and the effect observed in the present study occurs four days after T. lewisi infection, a relation between both events, immunosuppressive action and epimastigote extracts can be established. This immune effect could be the result of a INF-g reduction after 4 or 5 days after T. lewisi infection and not due to an IL-2 inhibition as suggested by Ndarathi13. Production of IL-10 is another possibility since it has been shown that this lymphokine can be secreted as response to T. congolense extracts6. More studies on this model are currently in progress.

 

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Acknowledgement: This work was supported by the project 803-A2-045 from the Research Vicerectory, University of Costa Rica.

 

Address for correspondence: Misael Chinchilla Ph.D. Facultad de Microbiología, Universidad de Costa Rica. San José, Costa Rica. América Central. Tel. 506-2074277 Fax: 506-2252374.