Pathogenesis of Chagas disease cardiomyopathy

Table 1 Molecular mimicry after Trypanosoma cruzi infection

Host component	T. cruzi antigen	Host	Molecular definition
Neurons, liver, Kidney, testis	?	M, R	Mab
Neurons	Sulphated glycolipids	H, R	Mab, sera
47 kDa neuron protein	FL 160	H, R	rDNA, AS
Heart and skeletal muscle	Microsomal fraction	H, M	Mab, Serum IgG
Smooth and striated muscle	150 kDa protein	H, M	Serum IgG
Human cardiac Myosin heavy chain	B13 protein	H	rDNA, Ab T cell clones
Human cardiac myosin heavy chain	Cruzipain	M	Ab
95 KDa myosin tail	T. cruzi cytoskeleton	M	Mab
Skeletal muscle Ca++ dependent SRA	SRA	H, Rb	AS, serum IgG
Glycosphingolipids	Glycosphingolipids	H, M	Serum IgG
MAP (brain)	MAP	H, M	rDNA, AS
Myelin basic protein	T. cruzi soluble extract	M	Serum IgG, T cells
28 kDa lymphocyte membrane protein	55 kDa membrane protein	H, M	Mab
23 kDa ribosomal protein	23 kDa ribosomal protein	H	Ab
Ribosomal P protein	Ribosomal P protein	H	rDNA, Ab, SP
38-kDa heart antigen	R13 peptide from ribosomal protein P1, P2	M	IgG1, IgG2
β1 adrenoreceptor M2 muscarinic receptor	Ribosomal P0 and P2 proteins	H	Ab, SP
β1-adrenoreceptor M2 cholinergic receptor	150 kDa protein	H, M	Mab
Cardiac muscarinic Acetylcholine receptors (mAChR)	?	H	Ab
Cardiac muscarinic Acetylcholine receptors (mAChR)	Cruzipain	M	Immunization with cruzipain
Cha antigen	SAPA, 36KDa TENU2845	M	Ab, T cells

M: Mouse; H: Human; Rb: Rabbit; R: Rat; AS; Antiserum; Ab: Patient antibody; Mab: Monoclonal antibody; rDNA: Recombinant DNA; SP: Synthetic peptides (adapted from Bilate and Cunha-Neto[6] and Cunha-Neto et al[120]). SRA: Cross-reacting antigen; MAP: Microtubule associated protein. T. Cruzi: Trypanosoma cruzi.

Table 2 Cytokine and chemokine expression in Chagas disease and animal models

Cytokines/chemokines	Phase (acute/chronic/IND/severe/moderate CCC)	Host (mouse/human)	Organ/cell type	Reference
IFN-γ	Severe CCC	Human	Mononuclear cells	[54,56]
IFN-γ	Severe CCC	Human	Myocardium	[60,61]
IFN-γ	Severe CCC	Human	Heart-infiltrating T cells	[54]
IFN-γ	IND, Severe CCC	Human	Plasma	[52,54,55]
TNF-α	Severe CCC	Human	Mononuclear cells	[54, 56]
TNF-α	Severe CCC	Human	Heart-infiltrating T cells	[54]
TNF-α	Severe CCC	Human	Myocardium	[60, 61]
TNF-α	IND and Severe CCC	Human	Plasma	[52,54,55]
IFN-γ	Acute/chronic	Mouse	Heart	[121-123]
TNF-α	Acute/chronic	Mouse	Heart	[124]
IL-6	Severe CCC	Human	HEART-infiltrating T cells	[54,60,61]
IL-2	Severe CCC	Human	Heart-infiltrating T cells	[54,60,61]
IL-4	Severe CCC	Human	Heart-infiltrating T cells	[54,60,61]
IL-10	Severe CCC	Human	Heart-infiltrating T cells	[54,60,61]
IL-7	Severe CCC	Human	Myocardium	[62]
IL-15	Severe CCC	Human	Myocardium	[62]
IL-12	Acute	Mouse	Mononuclear cells	[125]
IL-18	Acute	Mouse	Mononuclear cells	[126]
IL-10	Acute	Mouse	Mononuclear cells	[44-46]
TGF-β	Acute	Mouse	Mononuclear cells	[44-46]
IL-17	Chronic	Mouse	Mononuclear cells	[47]
CCL2, CXCL10, CXCL9 (mRNA)	Severe CCC	Human	Myocardium	[59]
CCR2, CXCR3 (mRNA)	Severe CCC	Human	Myocardium	[59]
CCR5, CXCR3	Severe CCC, IND	Human	Mononuclear cells	[63]
CCL5, CXCL9, CXCL10	Chronic	Mouse	Cardiomyocytes	[127]
CCR5	Chronic	Mouse	Heart	[40,128]
CCL5, CCL4, CXCR3 (mRNA)	Chronic	Dog	Heart	[41]

CCC: Chronic Chagas disease cardiomyopathy; IND: Indeterminate clinical form; IFN: Interferon; TNF: Tumor necrosis factor; IL: Interleukin.

Table 3 Case control studies done on the TNFA-308 polymorphism

Study name	Cases No. of chr carrying the TNFA-308T2 allele	Cases Total No. of chromosome	Controls No. of chr carrying the TNFA-308T2 allele	Controls Total No. of chromosome
Rodriguez-Perez et al[96]	13	108	14	324
Drigo et al[98]	37	332	16	160
Beraun et al[99]	5	66	4	104