We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genetic and Functional Role of TNF-alpha in the Development Trypanosoma cruzi Infection.
- Authors
Pissetti, Cristina Wide; Correia, Dalmo; de Oliveira, Rafael Faria; Llaguno, Maurício Manoel; Balarin, Marly Aparecida Spadotto; Silva-Grecco, Roseane Lopes; Rodrigues Jr, Virmondes
- Abstract
TNF-alpha plays an important role in trypanocidal mechanisms and is related to tissue injury. This cytokine has been detected in the heart of human chagasic patients where it is associated with tissue damage. This study investigated whether TNF-alpha levels and the presence of genetic polymorphisms are associated with the presence of T. cruzi infection and/or with the development of the cardiac form in chronic chagasic patients. Genomic DNA of 300 subjects from an endemic area was extracted and analyzed by PCR using specific primers. TNF-alpha was assayed in culture supernatants by ELISA. An association was observed between the absence of the TNF-238A allele and negative serology. Furthermore, seropositive individuals carrying the TNF-238A allele produced significantly higher TNF-alpha levels without stimulation (p = 0.04) and after stimulation with LPS (p = 0.007) and T. cruzi antigens (p = 0.004). The present results suggest that the polymorphism at position -238 influences susceptibility to infection and that this allele is associated with higher TNF-alpha production in seropositive individuals. Author Summary: Chagas disease is an important parasitic disease that has no cure. The pathogenesis of the disease is still not completely understood. Studies using candidate genes are important to better understand the differences between individuals that lead to such heterogenous disease. TNF-alpha is a cytokine involved in the control of parasitemia during the acute phase and in cardiac injury during the chronic phase. The TNF-alpha gene is located in an important region of the MHC and its polymorphisms are associated with many parasitic and infectious diseases such as cerebral malaria and leishmaniasis. These studies are important since they were conducted in the same regions and involved populations leaving in the same conditions. The present study shows that patients with the indeterminate form produce higher levels of TNF-alpha than cardiac patients. The data suggest a control mechanism between inflammatory and regulatory cytokines. In addition, the presence of the TNF-238G allele contributes to the development of negative serology. We show that CD8+ T lymphocytes and macrophages are the main cells producing TNF-alpha. This study is an important contribution to explain the pathogenesis of Chagas disease.
- Subjects
TUMOR necrosis factors; TRYPANOSOMA cruzi; CEREBRAL malaria; CHAGAS' disease; PARASITIC diseases; CYTOTOXIC T lymphocyte-associated molecule-4; PARASITOLOGY
- Publication
PLoS Neglected Tropical Diseases, 2011, Vol 5, Issue 3, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0000976