Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is responsible for the highest disease burden of any parasitic disease in the Western Hemisphere and one of the leading causes of complications, including heart failure, and death in Latin America. Traditionally regarded as a tropical disease found only in Mexico, Central America, and South America, the disease now affects at least 300,000 residents of the United States and is growing in prevalence in other traditionally non-endemic areas, including Canada, Europe, Australia, and Japan.
Despite its prevalence, the pathogenesis of Chagas disease is complex and not thoroughly understood. Furthermore, very little is known about mechanisms of progression from asymptomatic T. cruzi infection to chronic Chagas cardiomyopathy. A large body of evidence implicates inflammation, including dysfunctional innate and adaptive immunity, in the immunopathogenesis of the disease. Several biomarkers have been reported in chronic Chagas disease, but most lack the underlying relevance for the pathogenesis of the disease.
Deciphering the cellular and molecular mechanisms associated with the pathogenesis of Chagas disease could aid in the identification of patients at the highest risk for progression to chronic Chagas cardiomyopathy and contribute to improving the outcomes of millions of people living with the disease.
To this end, this Research Topic will gather basic and translational research that provide novel insights into cellular and molecular mechanisms of the immune system implicated in the pathogenesis of Chagas disease, and how this knowledge can be translated to clinical practice and help reduce the burden of complications, and ultimately contributing to improving adverse outcomes. Submission of Original Research, Brief Research Report, and Review articles is welcome.
Specific areas to cover may include:
1) Innate immunity to T. cruzi infection
• Activation of phagocytes (monocytes, macrophages, neutrophils, and dendritic cells) and cytokine/chemokine-mediated immune response
• Natural killer cells: Their receptors and function in lymphocytes and parasite clearance
• Reactive oxygen species and cell signaling
• Role of host-derived nitro-oxidative stress
• Effector mechanisms of the complement system
• Role of costimulatory molecules
• Signaling pathways and role of Toll-like receptors: Perspectives for vaccine development
2) Humoral immunity to T. cruzi infection
• Biological relevance of epitope cross-reactivity to T. cruzi antigens
• B and T cell tolerance and autoimmunity
3) Adaptive immunity to T. cruzi infection
• B cell-mediated immune response: Antibody/cytokine secretion, antigen presentation, and regulatory functions
• T cell-mediated immune response (memory T cells, CD4+ T cells; CD8+ cytolytic T lymphocytes)
• Helper T cells and immunoregulatory networks (TH1/TH2/TH17 responses)
4) The role of plasma-membrane-derived vesicles (e.g. ectosomes and exosomes) and cell-derived molecules, such as lipoproteins, peptides, and nucleic acids (e.g. miRNAs and mRNAs) in Chagas disease.
5) Single cell and RNA sequencing analysis
• Single-cell genomics to dissect the immunobiology of Chagas cardiomyopathy
• Analysis of the pre-mRNA processing sites
• Analysis of single-nucleus transcriptomes and transcriptional responses
• Novel disease-associated transcriptomic subpopulations
6) Genetic and epigenetic control of immune response to T. cruzi infection and pathogenesis of Chagas disease
7) Neuroimmunomodulation and immune-metabolic markers
8) Matrix metalloproteinases and immune system
Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is responsible for the highest disease burden of any parasitic disease in the Western Hemisphere and one of the leading causes of complications, including heart failure, and death in Latin America. Traditionally regarded as a tropical disease found only in Mexico, Central America, and South America, the disease now affects at least 300,000 residents of the United States and is growing in prevalence in other traditionally non-endemic areas, including Canada, Europe, Australia, and Japan.
Despite its prevalence, the pathogenesis of Chagas disease is complex and not thoroughly understood. Furthermore, very little is known about mechanisms of progression from asymptomatic T. cruzi infection to chronic Chagas cardiomyopathy. A large body of evidence implicates inflammation, including dysfunctional innate and adaptive immunity, in the immunopathogenesis of the disease. Several biomarkers have been reported in chronic Chagas disease, but most lack the underlying relevance for the pathogenesis of the disease.
Deciphering the cellular and molecular mechanisms associated with the pathogenesis of Chagas disease could aid in the identification of patients at the highest risk for progression to chronic Chagas cardiomyopathy and contribute to improving the outcomes of millions of people living with the disease.
To this end, this Research Topic will gather basic and translational research that provide novel insights into cellular and molecular mechanisms of the immune system implicated in the pathogenesis of Chagas disease, and how this knowledge can be translated to clinical practice and help reduce the burden of complications, and ultimately contributing to improving adverse outcomes. Submission of Original Research, Brief Research Report, and Review articles is welcome.
Specific areas to cover may include:
1) Innate immunity to T. cruzi infection
• Activation of phagocytes (monocytes, macrophages, neutrophils, and dendritic cells) and cytokine/chemokine-mediated immune response
• Natural killer cells: Their receptors and function in lymphocytes and parasite clearance
• Reactive oxygen species and cell signaling
• Role of host-derived nitro-oxidative stress
• Effector mechanisms of the complement system
• Role of costimulatory molecules
• Signaling pathways and role of Toll-like receptors: Perspectives for vaccine development
2) Humoral immunity to T. cruzi infection
• Biological relevance of epitope cross-reactivity to T. cruzi antigens
• B and T cell tolerance and autoimmunity
3) Adaptive immunity to T. cruzi infection
• B cell-mediated immune response: Antibody/cytokine secretion, antigen presentation, and regulatory functions
• T cell-mediated immune response (memory T cells, CD4+ T cells; CD8+ cytolytic T lymphocytes)
• Helper T cells and immunoregulatory networks (TH1/TH2/TH17 responses)
4) The role of plasma-membrane-derived vesicles (e.g. ectosomes and exosomes) and cell-derived molecules, such as lipoproteins, peptides, and nucleic acids (e.g. miRNAs and mRNAs) in Chagas disease.
5) Single cell and RNA sequencing analysis
• Single-cell genomics to dissect the immunobiology of Chagas cardiomyopathy
• Analysis of the pre-mRNA processing sites
• Analysis of single-nucleus transcriptomes and transcriptional responses
• Novel disease-associated transcriptomic subpopulations
6) Genetic and epigenetic control of immune response to T. cruzi infection and pathogenesis of Chagas disease
7) Neuroimmunomodulation and immune-metabolic markers
8) Matrix metalloproteinases and immune system
