PLoS Neglected Tropical Diseases (Jan 2011)

Genetic and functional role of TNF-alpha in the development Trypanosoma cruzi infection.

  • Cristina Wide Pissetti,
  • Dalmo Correia,
  • Rafael Faria de Oliveira,
  • Maurício Manoel Llaguno,
  • Marly Aparecida Spadotto Balarin,
  • Roseane Lopes Silva-Grecco,
  • Virmondes Rodrigues

DOI
https://doi.org/10.1371/journal.pntd.0000976
Journal volume & issue
Vol. 5, no. 3
p. e976

Abstract

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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.