Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease

Marcus Paulo Ribeiro Machado, Aletheia Moraes Rocha, Lucas Felipe de Oliveira, Marília Beatriz de Cuba, Igor de Oliveira Loss, Lucio Roberto Castellano, Marcus Vinicius Silva, Juliana Reis Machado, Gabriel Antonio Nogueira Nascentes, Luciano Henrique Paiva, Wilson Savino, Virmondes Rodrigues Junior, Patricia Chakur Brum, Vania Ferreira Prado, Marco Antonio Maximo Prado, Eliane Lages Silva, Nicola Montano, Luis Eduardo Ramirez, Valdo Jose Dias da Silva

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1186-1202
Number of pages17
JournalExperimental Physiology
Issue number11
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Physiology


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