Table 1.

Intestinal microenvironment and biological behavior of the components involved in the pathophysiology of Chagasic megacolon.

Biomarker or techniques	Markers	Behavior	Supposed participation in the pathogenesis	References
PGP 9.5	Pan-neural	↓	Destruction induced by the parasite and the inflammatory process established in the intestine. It affects intestinal motility and is involved with fecal stasis, organ dilation, and Chagasic megacolon progression.	[15, 34]
Peripherin	Pan-neural	↓		[50, 112]
	Disregarded	-		[48, 57]
HuC/HuDa	Pan-neural	↓		[56]
Substance P	Excitatory motor neurons (SP)	↑	Maintenance of the intestinal proinflammatory profile.	[56, 77]
GAP-43	Excitatory motor neuron regeneration (GAP-43/SP and GAP-43/cCHAT)	=	The greatest regeneration found in the subpopulations of inhibitory motor neurons (GAP-43/VIP and GAP-43/NO) is related to the greater destruction of these cell types when compared to the other subpopulations, which do not suffer reduction. Thus, through compensatory mechanisms, the subpopulation of inhibitory neurons tries to be reestablished, and due to this, there is only an increase in this subpopulation.	[50]
	Inhibitory motor neuron regeneration (GAP-43/VIP and GAP-43/NO)	↑
	Intrinsic primary afferent neuron regeneration (GAP-43/calretinin)	=
	Interneuron regeneration (GAP-43/neuropeptide Y)	=
S-100	Enteric glial cells	↓	Infection focus in the intestine.	[15, 21, 114]
GFAP	Enteric activated glial cells	↑	Increased activation of this cell type in an attempt to control the infection through the production of proinflammatory and microbicidal components, which leads to neurotoxicity or/and increased activation of this cell type in an attempt to control the inflammatory process through the production of anti and regulatory cytokines and neuroprotective components.	[15, 21]
CD3+	T lymphocyte	↑	Participation of the immune response in neuronal loss.	[8, 15]
CD20+	B lymphocyte	↑
CD68+	Macrophage	↑		[15]
CD57+	Natural killer cell	↑
TIA-1+	Cytotoxic lymphocyte	↑
Hematoxylin–eosin section	Eosinophil	↑	Participation of the immune response in neuronal loss and intestinal remodeling.	[13]
Giemsa/toluidine blue section	Mast cell	↑		[13, 139]
Serotonin	Serotonin-producing cells	↓	Duality between the anti-inflammatory and proinflammatory role of the components.	[138, 211]
		↑		[32]
5-HT3a receiver	Lymphocytes producing 5-HT3a receptor	↓		[212]
Tryptase	Tryptase-producing mast cells	↑	Participation in neuronal damage, maintenance of the inflammatory process, and tissue remodeling in the intestine.	[34, 158]
Chymase	Chymase-producing mast cells	↑		[34]
Galectin-1 and -9	Galectins	↑	Neuroprotection and infection control.	[182]
Galectin-3	Galectins	↑	Maintenance of the inflammatory process, neuroinflammation, and fibrosis.	[182, 183]

↑: increased component compared to healthy intestine without T. cruzi infection; ↓: decreased component compared to healthy intestine without T. cruzi infection; =: no component change compared to healthy intestine without T. cruzi infection.