NOD2 receptor is crucial for protecting against the digestive form of Chagas disease

Area of Science:

• Immunology
• Infectious Diseases
• Gastroenterology

Background:

• Digestive and cardiodigestive forms of Chagas' disease affect 2-27% of patients.
• The pathogenesis of digestive Chagas' disease involves complex immunopathological responses.
• The role of the NOD2 innate immune receptor in digestive Chagas' disease remains unclear.

Purpose of the Study:

• To investigate the role of the NOD2 innate immune receptor in the pathogenesis of digestive Chagas' disease.
• To compare NOD2 expression in patients with digestive versus indeterminate forms of Chagas' disease.
• To evaluate the impact of NOD2 deficiency on Chagas' disease progression in a mouse model.

Main Methods:

• Real-time PCR analysis of peripheral blood mononuclear cells from Chagas' disease patients.
• Correlation analysis between NOD2 expression and clinical parameters (esophageal, sigmoid, and rectal dilation).
• Infection of NOD2 knockout mice with Trypanosoma cruzi and subsequent assessment of intestinal motility and histopathology.

Main Results:

• Patients with digestive Chagas' disease exhibited lower NOD2 mRNA expression and higher RIP2 and alpha-defensin 6 expression compared to those with indeterminate forms.
• A negative correlation was observed between NOD2 expression and the degree of dilation in the esophagus, sigmoid, and rectum.
• NOD2 knockout mice infected with T. cruzi showed decreased intestinal motility and exacerbated inflammation and muscle layer hypertrophy in the colon and jejunum during the chronic phase.

Conclusions:

• NOD2 plays a protective role in preventing the development of the digestive form of Chagas' disease.
• NOD2 deficiency exacerbates Chagas' disease-associated gastrointestinal pathology.
• Targeting NOD2 signaling may offer a therapeutic strategy for digestive Chagas' disease.