Different infective forms trigger distinct immune response in experimental Chagas disease.

Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease

Cytokine profile of spleen T-lymphocytes from mice before (0) and at 7, 14, 28 and 42 days after infection with metacyclic (MT) or blood trypomastigotes (BT) of <i>Trypanosoma cruzi</i>.

<p>“Gray scale” diagrams were used to represent the cytokine pattern and the cytokine balance within T-cell subsets besides the overall cytokine balance with T-cells, highlighting the predominance of “low” cytokine-producers (white square), “high” TNF-α or IFN-γ producers (black square), “high” IL-10⁺ producers (light gray square) or “high” mixed cytokine-producers (dark gray square). Pie charts represent the percentage of animals displaying a given T-cells overall cytokine balance selectively amongst the “high” cytokine-producers. ND = Not detected.</p

Morphometric analysis and photomicrographs of the area of <i>T. cruzi</i> immunoreactions in the heart at 28 days after mice infection with metacyclic (MT; light gray bar) or blood trypomastigotes (BT; black bar) of <i>Trypanosoma cruzi</i>.

<p>Analysis of the area of <i>T. cruzi</i> amastigotes were identified by immunohistochemistry as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032912#s4" target="_blank">Material and Methods</a>. The results are expressed as parasited area ± standard error. Photomicrographs of the heart parasitism demonstrating isolated amastigotes in MT and typical amastigote nests in BT.</p