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

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

来源：Experimental Physiology, 2012, 97(11): 1186-1202.

DOI：10.1113/expphysiol.2012.066431

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 beta(2)-adrenergic receptor knockout (KO beta 2) FVB mice. During infection and at 1821 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 KO beta 2-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 KO beta 2 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.

• 出版日期2012-11