Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host’s immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions.

This study was designed to determine whether the functional IL-10 gene polymorphism -1082G/A is associated with the development of cardiomyopathy in individuals infected with Trypanosoma cruzi and whether interleukin (IL)-10 expression can be correlated with patients' cardiac function. Our results demonstrated that the polymorphic allele, which correlates with lower expression of IL-10, was associated with the development of Chagas disease cardiomyopathy. Accordingly, correlative analysis showed that low IL-10 expression was associated with worse cardiac function, as determined by left-ventricular ejection fraction values. Therefore, the IL-10 gene polymorphism and IL-10 expression are important in determining susceptibility to chagasic cardiomyopathy.

ABSTRACT.Purpose: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans. Methods: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus )174 of IL-6 ()174G ⁄ C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes. Results: There was a significant difference in the genotype (v 2 = 12.9, p = 0.001) and allele (v 2 = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence. Conclusions: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR.

The interaction between the protozoan parasite Trypanosoma cruzi and the human host dates back 9000 years, as demonstrated by molecular analysis of material obtained from Andean mummies indicating the presence of the parasite’s kinetoplast DNA in populations from Chile and Peru. This long-established interaction, which persists today, demonstrates that T. cruzi has established a very well adapted relationship with the human host. From a host-parasite relationship point-of-view this is desirable, however, such a high degree of adaptation is perhaps the foundation for many of the unknowns that surround this disease. Unveiling of the immunological mechanisms that underlie the establishment of pathology, identification of parasite-associated factors that determine strain-differential tissue tropism, discovery of host genetic elements that influence the development of different clinical forms of the disease, and understanding environmental factors that may influence the host-parasite interactions, are some of the key questions remaining to be answered. The response to these questions will aid in addressing some of the current challenges in Chagas disease: fulfilling the need for efficient diagnosis, developing effective prophylactic measures, discovering effective therapeutics, and finding methods to control disease progression.

This is the first study to investigate the association between TNF-alpha polymorphism and the occurrence of TR in humans. TNF-alpha gene polymorphism (-308G/A) does not seem to be associated with the occurrence or recurrence of TR.