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Published on: November 3, 2014
Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in
Nathalie de Sena Pereira1,2,3, Tamyres Bernadete Dantas Queiroga2, Daniela Ferreira Nunes1
1Department of Parasitology, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, Brazil.
Insights
Innate immune receptors like Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are linked to Chagas disease complications. Their elevated expression correlates with cardiac and digestive dysfunction in patients with chronic Chagas disease.
Area of Science:
- Immunology
- Infectious Diseases
- Cardiology
Background:
- Chronic chagasic cardiomyopathy (CCC) is a major cause of death in Chagas disease.
- The role of innate immunity, specifically Toll-like receptors (TLRs) and Nod-like receptors (NLRs), in CCC pathophysiology remains unclear.
- Understanding innate immune responses is crucial for managing Chagas disease progression.
Purpose of the Study:
- To investigate the association between innate immune receptors (TLR1-9, NLRP3), adapter molecules, and cytokines with clinical manifestations in chronic Chagas disease.
- To determine the relationship between these immune markers and cardiac and digestive function.
- To elucidate the role of innate immunity in the pathogenesis of CCC and digestive complications.
Main Methods:
- Evaluated mRNA expression of TLRs, NLRs, adapter molecules (Myd88, TRIF, ASC, caspase-1), and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, IFN-β) in patients with different forms of chronic Chagas disease.
- Correlated immune marker expression with clinical data, including cardiac and digestive function.
- Utilized peripheral blood mononuclear cells (PBMCs) for gene expression analysis.
Main Results:
- Elevated TLR8 and IFN-β mRNA expression observed in digestive and cardiodigestive patients, correlating with sigmoid and rectum size.
- Increased TLR2, IL-12, and TNF-α mRNA expression in cardiac and cardiodigestive patients.
- Higher NLRP3, ASC, and IL-1β mRNA levels found in cardiac patients compared to indeterminate cases.
- Negative correlations between TLR2, IL-1β, IL-12, TNF-α and left ventricular ejection fraction; positive correlations with cardiac and left ventricular mass indices.
Conclusions:
- High expression of innate immune receptors (TLRs, NLRP3) and associated cytokines contributes to cardiac and digestive dysfunction in Chagas disease.
- Specific TLRs and NLRs are implicated in the distinct clinical manifestations of chronic Chagas disease.
- Innate immunity plays a significant role in the pathogenesis of chronic chagasic cardiomyopathy and digestive complications.
Abstract:
Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction.
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