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Aspectos imunológicos da infecção experimental em camundongos por formas tripomastigotas metacíclicas ou sanguíneas do Trypanosoma cruzi.

Paula Melo de Abreu Vieira

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Abstract

The metacyclic and blood trypomastigotes of Trypanosoma cruzi are fully functional in relation to the parasite-host interaction and / or invasion of target cells, though they differ in the molecules present on their surfaces. Thus, issues related to variability in how the infective forms of T. cruzi interacts with host cells may lead to fundamental implications in the immune response against the parasite and, consequently, the clinical evolution of Chagas disease. The recent increase in the number of chagasic imigrants in non-endemic countries makes important to know what is the impact of infection by blood forms in the course of the disease. Thus, the study of infection by different infective forms of T. cruzi during the acute phase of infection, leads to a better understanding of the mechanisms involvcd in the pathogenesis of Chagas disease. Based on this, the goal of this work was to evaluate changes related to cellular immune parameters during acute experimental infection of mice by metacyclic trypomastigotes (TM) or blood (BT) of Trypanosoma cruzi Berenice-78 strain. The animals in the BT group showed an earlier and higher levels of parasitemia when compared with the group MT during the 42 days evaluated. Analysis of peripheral blood leukocytes demonstrated that infection by a BT forms leads to a bimodal profile, with an increase of leukocytes in the 7th and 42nd days after the infection, while infection by MT forms leads to a unimodal profile, with an increase in these cells occurring later in the 28th and 42nd days after infection. The assessment on intracytoplasmic cytokine production by splenocytes demonstrated that in the infection with BT forms occurs an early production of TNF- accompanied by a later production of IFN-, when the parasitemia is already under control. A different profile was seen in infection by MT forms, which presents an early production of IFN-. Moreover, in the BT group does not occur a reversal of the inflammatory profile to an immunomodulator profile, even when the parasitemia is already under control, which happens in animals infected with metacyclic forms. These data corroborate with the quantification of cardiac inflammatory infiltration, in which the animals in the BT group showed an earlier inflammation (day 7 after infection) which remained high until the 42nd day after infection, demonstrating that in these animals there is an exacerbation of inflammatory process. In the animals of MT group was observed a reduction in cardiac inflammation at the 42nd day after infection, thus confirming that the infection by MT forms can control inflammation. The histological analysis of spleen, also showed greater severity in the BT group. Therefore, the initial interaction between metacyclic trypomastigotes and vertebrate host induces an immune response profile different from that observed in infections with blood trypomastigotes. Thus, it is observed that infection by metacyclic trypomastigotes occurs more quietly, promoting an immune response capable of controlling not only the number of parasites during the acute phase of infection but also to establish an immunoregulatory response at the end of the acute phase , thus limiting the development of lesions associated with Chagas disease. However, infection with blood trypomastigotes occurs in a more alarming and in spite of control of parasitemia, the establishment of an effective immunoregulatory response does not occur, thus leading to persistent inflammation is present.

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What this paper is about

The metacyclic and blood trypomastigotes of Trypanosoma cruzi are fully functional in relation to the parasite-host interaction and / or invasion of target cells, though they differ in the molecules present on their surfaces. Thus, issues related to variability in how the infective forms of T. cruzi interacts with host cells may lead to fundamental implications in the immune response against the parasite and, consequently, the clinical evolution of Chagas disease. The recent increase in the number of chagasic imigrants in non-endemic countries makes important to know what is the impact of infection by blood forms in the course of the disease. Thus, the study of infection by different infective forms of T. cruzi during the acute phase of infection, leads to a better understanding of the mechanisms involvcd in the pathogenesis of Chagas disease. Based on this, the goal of this work was to evaluate changes related to cellular immune parameters during acute experimental infection of mice by metacyclic trypomastigotes (TM) or blood (BT) of Trypanosoma cruzi Berenice-78 strain. The animals in the BT group showed an earlier and higher levels of parasitemia when compared with the group MT during the 42 days evaluated. Analysis of peripheral blood leukocytes demonstrated that infection by a BT forms leads to a bimodal profile, with an increase of leukocytes in the 7th and 42nd days after the infection, while infection by MT forms leads to a unimodal profile, with an increase in these cells occurring later in the 28th and 42nd days after infection. The assessment on intracytoplasmic cytokine production by splenocytes demonstrated that in the infection with BT forms occurs an early production of TNF- accompanied by a later production of IFN-, when the parasitemia is already under control. A different profile was seen in infection by MT forms, which presents an early production of IFN-. Moreover, in the BT group does not occur a reversal of the inflammatory profile to an immunomodulator profile, even when the parasitemia is already under control, which happens in animals infected with metacyclic forms. These data corroborate with the quantification of cardiac inflammatory infiltration, in which the animals in the BT group showed an earlier inflammation (day 7 after infection) which remained high until the 42nd day after infection, demonstrating that in these animals there is an exacerbation of inflammatory process. In the animals of MT group was observed a reduction in cardiac inflammation at the 42nd day after infection, thus confirming that the infection by MT forms can control inflammation. The histological analysis of spleen, also showed greater severity in the BT group. Therefore, the initial interaction between metacyclic trypomastigotes and vertebrate host induces an immune response profile different from that observed in infections with blood trypomastigotes. Thus, it is observed that infection by metacyclic trypomastigotes occurs more quietly, promoting an immune response capable of controlling not only the number of parasites during the acute phase of infection but also to establish an immunoregulatory response at the end of the acute phase , thus limiting the development of lesions associated with Chagas disease. However, infection with blood trypomastigotes occurs in a more alarming and in spite of control of parasitemia, the establishment of an effective immunoregulatory response does not occur, thus leading to persistent inflammation is present.

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Available abstract

The metacyclic and blood trypomastigotes of Trypanosoma cruzi are fully functional in relation to the parasite-host interaction and / or invasion of target cells, though they differ in the molecules present on their surfaces. Thus, issues related to variability in how the infective forms of T. cruzi interacts with host cells may lead to fundamental implications in the immune response against the parasite and, consequently, the clinical evolution of Chagas disease. The recent increase in the number of chagasic imigrants in non-endemic countries makes important to know what is the impact of infection by blood forms in the course of the disease. Thus, the study of infection by different infective forms of T. cruzi during the acute phase of infection, leads to a better understanding of the mechanisms involvcd in the pathogenesis of Chagas disease. Based on this, the goal of this work was to evaluate changes related to cellular immune parameters during acute experimental infection of mice by metacyclic trypomastigotes (TM) or blood (BT) of Trypanosoma cruzi Berenice-78 strain. The animals in the BT group showed an earlier and higher levels of parasitemia when compared with the group MT during the 42 days evaluated. Analysis of peripheral blood leukocytes demonstrated that infection by a BT forms leads to a bimodal profile, with an increase of leukocytes in the 7th and 42nd days after the infection, while infection by MT forms leads to a unimodal profile, with an increase in these cells occurring later in the 28th and 42nd days after infection. The assessment on intracytoplasmic cytokine production by splenocytes demonstrated that in the infection with BT forms occurs an early production of TNF- accompanied by a later production of IFN-, when the parasitemia is already under control. A different profile was seen in infection by MT forms, which presents an early production of IFN-. Moreover, in the BT group does not occur a reversal of the inflammatory profile to an immunomodulator profile, even when the parasitemia is already under control, which happens in animals infected with metacyclic forms. These data corroborate with the quantification of cardiac inflammatory infiltration, in which the animals in the BT group showed an earlier inflammation (day 7 after infection) which remained high until the 42nd day after infection, demonstrating that in these animals there is an exacerbation of inflammatory process. In the animals of MT group was observed a reduction in cardiac inflammation at the 42nd day after infection, thus confirming that the infection by MT forms can control inflammation. The histological analysis of spleen, also showed greater severity in the BT group. Therefore, the initial interaction between metacyclic trypomastigotes and vertebrate host induces an immune response profile different from that observed in infections with blood trypomastigotes. Thus, it is observed that infection by metacyclic trypomastigotes occurs more quietly, promoting an immune response capable of controlling not only the number of parasites during the acute phase of infection but also to establish an immunoregulatory response at the end of the acute phase , thus limiting the development of lesions associated with Chagas disease. However, infection with blood trypomastigotes occurs in a more alarming and in spite of control of parasitemia, the establishment of an effective immunoregulatory response does not occur, thus leading to persistent inflammation is present.

Key concepts: Parasitemia, Trypanosoma cruzi, Chagas disease, Biology, Immune system, Parasite hosting, Pathogenesis, Immunology

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Aspectos imunológicos da infecção experimental em camundongos por formas tripomastigotas metacíclicas ou sanguíneas do Trypanosoma cruzi. — Research Paper | ScholarLens