Abstract
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 β2-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.
| Original language | English |
|---|---|
| Pages (from-to) | 1186-1202 |
| Number of pages | 17 |
| Journal | Experimental Physiology |
| Volume | 97 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2012 |
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- Physiology
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Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease. / Machado, Marcus Paulo Ribeiro; Rocha, Aletheia Moraes; de Oliveira, Lucas Felipe; de Cuba, Marília Beatriz; de Oliveira Loss, Igor; Castellano, Lucio Roberto; Silva, Marcus Vinicius; Machado, Juliana Reis; Nascentes, Gabriel Antonio Nogueira; Paiva, Luciano Henrique; Savino, Wilson; Junior, Virmondes Rodrigues; Brum, Patricia Chakur; Prado, Vania Ferreira; Prado, Marco Antonio Maximo; Silva, Eliane Lages; Montano, Nicola; Ramirez, Luis Eduardo; Dias da Silva, Valdo Jose.
In: Experimental Physiology, Vol. 97, No. 11, 11.2012, p. 1186-1202.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease
AU - Machado, Marcus Paulo Ribeiro
AU - Rocha, Aletheia Moraes
AU - de Oliveira, Lucas Felipe
AU - de Cuba, Marília Beatriz
AU - de Oliveira Loss, Igor
AU - Castellano, Lucio Roberto
AU - Silva, Marcus Vinicius
AU - Machado, Juliana Reis
AU - Nascentes, Gabriel Antonio Nogueira
AU - Paiva, Luciano Henrique
AU - Savino, Wilson
AU - Junior, Virmondes Rodrigues
AU - Brum, Patricia Chakur
AU - Prado, Vania Ferreira
AU - Prado, Marco Antonio Maximo
AU - Silva, Eliane Lages
AU - Montano, Nicola
AU - Ramirez, Luis Eduardo
AU - Dias da Silva, Valdo Jose
PY - 2012/11
Y1 - 2012/11
N2 - 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 β2-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.
AB - 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 β2-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.
UR - http://www.scopus.com/inward/record.url?scp=84867917649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867917649&partnerID=8YFLogxK
U2 - 10.1113/expphysiol.2012.066431
DO - 10.1113/expphysiol.2012.066431
M3 - Article
C2 - 22707503
AN - SCOPUS:84867917649
VL - 97
SP - 1186
EP - 1202
JO - Experimental Physiology
JF - Experimental Physiology
SN - 0958-0670
IS - 11
ER -