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Updated: May 18, 2026
Parasite Induced Genetically Driven Autoimmune Chagas Heart Disease in the Chicken Model
Published on: July 29, 2012
Parasite induced genetically driven autoimmune Chagas heart disease in the chicken model
Antonio R L Teixeira1, Nadjar Nitz, Francisco M Bernal
1Chagas Disease Multidisciplinary Research Laboratory, University of Brasilia. ateixeir@unb.br
Insights
Trypanosoma cruzi infection can lead to Chagas disease years later. This study shows parasite DNA integration into host genomes can trigger autoimmune responses, causing conditions like myocarditis and heart failure in chickens.
Area of Science:
- Immunology
- Genetics
- Parasitology
Background:
- Chagas disease pathogenesis is debated, with autoimmunity and parasite persistence as leading theories.
- Trypanosoma cruzi infections are often asymptomatic in childhood but can lead to chronic Chagas disease decades later.
- Understanding the mechanisms driving chronic Chagas disease is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the roles of parasite persistence and autoimmunity in Chagas disease pathogenesis.
- To determine if parasite DNA integration into the host genome can induce autoimmune responses.
- To establish a model for studying genetically driven autoimmune diseases.
Main Methods:
- Inoculation of Trypanosoma cruzi into fertilized chicken eggs.
- Analysis of parasite DNA integration using TAIL-PCR, Southern hybridizations, cloning, and sequencing.
- Assessment of immune responses and genetic alterations in kDNA-mutated chickens.
Main Results:
- Chicken immune systems eradicate T. cruzi, but parasite mitochondrial kinetoplast DNA (kDNA) minicircles integrate into the host genome.
- kDNA integrations disrupt gene functions related to cell physiology and immune response.
- kDNA-mutated chickens develop severe myocarditis, inflammatory cardiomyopathy, heart failure, and skeletal muscle weakness, mimicking human Chagas disease.
Conclusions:
- Trypanosoma cruzi infection can induce genetically driven autoimmune disease through parasite DNA integration.
- This study provides evidence for autoimmunity as a key mechanism in Chagas disease pathogenesis.
- The chicken model offers insights into the genetic basis of autoimmune conditions triggered by protozoan infections.
Abstract:
The Trypanosoma cruzi acute infections acquired in infancy and childhood seem asymptomatic, but approximately one third of the chronically infected cases show Chagas disease up to three decades or later. Autoimmunity and parasite persistence are competing theories to explain the pathogenesis of Chagas disease. To separate roles played by parasite persistence and autoimmunity in Chagas disease we inoculate the T. cruzi in the air chamber of fertilized eggs. The mature chicken immune system is a tight biological barrier against T. cruzi and the infection is eradicated upon development of its immune system by the end of the first week of growth. The chicks are parasite-free at hatching, but they retain integrated parasite mitochondrial kinetoplast DNA (kDNA) minicircle within their genome that are transferred to their progeny. Documentation of the kDNA minicircle integration in the chicken genome was obtained by a targeted prime TAIL-PCR, Southern hybridizations, cloning, and sequencing. The kDNA minicircle integrations rupture open reading frames for transcription and immune system factors, phosphatase (GTPase), adenylate cyclase and phosphorylases (PKC, NF-Kappa B activator, PI-3K) associated with cell physiology, growth, and differentiation, and other gene functions. Severe myocarditis due to rejection of target heart fibers by effectors cytotoxic lymphocytes is seen in the kDNA mutated chickens, showing an inflammatory cardiomyopathy similar to that seen in human Chagas disease. Notably, heart failure and skeletal muscle weakness are present in adult chickens with kDNA rupture of the dystrophin gene in chromosome 1. Similar genotipic alterations are associated with tissue destruction carried out by effectors CD45+, CD8γδ+, CD8α lymphocytes. Thus this protozoan infection can induce genetically driven autoimmune disease.
