Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease.
The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and β(2)-adrenergic receptor knockout (KOβ2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOβ2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOβ2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.
Biological Sciences Institute, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.
Marcus Paulo Ribeiro
MP
Machado
Aletheia Moraes
AM
Rocha
Lucas Felipe
LF
de Oliveira
Marília Beatriz
MB
de Cuba
Igor
I
de Oliveira Loss
Lucio Roberto
LR
Castellano
Marcus Vinicius
MV
Silva
Juliana Reis
JR
Machado
Gabriel Antonio Nogueira
GA
Nascentes
Luciano Henrique
LH
Paiva
Wilson
W
Savino
Virmondes Rodrigues
VR
Junior
Patricia Chakur
PC
Brum
Vania Ferreira
VF
Prado
Marco Antonio Maximo
MA
Prado
Eliane Lages
EL
Silva
Nicola
N
Montano
Luis Eduardo
LE
Ramirez
Valdo Jose
VJ
Dias da Silva
D000208:Acute Disease; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology*; D004562:Electrocardiography / Q000379:methods; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018512:Parasitemia / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*
D018343:Receptors, Adrenergic, beta-2; D001262:Atenolol; D011433:Propranolol; D011729:Pyridostigmine Bromide