Immunopathological Aspects of ExperimentalTrypanosoma cruziReinfections

Abstract

Chagas disease is caused by Trypanosoma cruzi infection. Besides the host-related factors, such as immune response and genetic background, the parasite, strain, and occurrences of reinfection episodes, may influence disease outcome. Our results demonstrate that both the primary infection and the reinfection with the Colombiana strain are connected with lower survival rate of the mice. After reinfection, parasitaemia is approximately ten times lower than in primary infected animals. Only Colombiana, Colombiana/Colombiana, and Y/Colombiana groups presented amastigote nests in cardiac tissue. Moreover, the mice infected and/or reinfected with the Colombiana strain had more T. cruzi nests, more intense inflammatory infiltrate, and higher in situ expression of TNF-α and IFN-γ than Y strain. Antigen-stimulated spleen cells from infected and/or reinfected animals produced higher levels of TNF-α, IFN-γ, and IL-10. Our results reinforce the idea that Chagas disease outcome is influenced by the strain of the infective parasite, being differentially modulated during reinfection episodes. It highlights the need of control strategies involving parasite strain characterization in endemic areas for Chagas disease.

Upregulation of Cardiac IL-10 and Downregulation of IFN-γin Balb/c IL-4−/−in Acute Chagasic Myocarditis due to Colombian Strain ofTrypanosoma cruzi

“…Qualitative analysis classified infiltrate as predominantly mononuclear (macrophages and lymphocytes) or polymorphonuclear (neutrophils and eosinophils), according to the cellular type observed in more than 50% of the infiltrate. Semiquantitative analysis classified the inflammatory infiltrate in mild (involvement < 25% of the tissue), moderate (25%–50% of the tissue), or severe (involvement > 50% of the tissue) [25].…”

“…Our group had already pointed out that infected and reinfected animals with Colombian strain present a modulation of immune response leading to higher production of proinflammatory cytokines, such as IFN- γ and TNF- α , resulting in marked myocarditis and lower survival rate [25]. As Balb/c mice are usually good IL-4 producers [26] and due to IL-4 relevance in modulating response against infectious and parasitic agents, including chagasic cardiomyopathy, IL-4 −/− knockout animals were used to analyze if this cytokine has any influence on immune response modulation in mice infected with T. cruzi Colombian strain, which has marked myotropism in acute phase.…”

The effect of reinfection and mixed Trypanosoma cruzi infections on disease progression in mice

“…On the one hand, the generation of a parasitaemia following initial infection, with subsequent infections generating lower [21] or no parasitaemias in mice, and the observation of no significant increase in tissue damage in reinfected dogs independent of isolates utilised [41], are indicative of host immune protection. Conversely, other studies investigating reinfection have demonstrated a failure to protect mice [42], with the observation of an increased parasitaemia [30] and an increase in the severity of cardiac alterations and disease progression [20,43]. Subsequently, these alterations may lead to death of the host [31].…”

“…This genetic heterogeneity means that dissimilar outcomes from reinfection experiments may reflect differences in parasite virulence or in the host immune response to the different parasite genotypes utilised. While the use of reference or highly utilised genotypes such as the Y [31,43], Tulahuen [20] and Colombian strains [45] in previous reinfection studies was useful in order for comparisons to be drawn between studies, more studies involving diverse and previously uncharacterised genotypes are also required to expand our knowledge.…”

T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment

“…A sustained inflammatory response featuring progressive tissue damage and fibrosis-related repair leads to chronic cardiac disability due to destruction and rearrangement of cardiomyocytes, microvasculature damage, and contractile alterations (12). Murine reinfections by T. cruzi are associated with cardiac damage and higher levels of inflammatory cytokines (13). In humans, the cellular immune response pattern seems to be related, at least in part, to the clinical forms.…”