A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

Daniela Carnevale, Marialuisa Perrotta, Fabio Pallante, Valentina Fardella, Roberta Iacobucci, Stefania Fardella, Lorenzo Carnevale, Raimondo Carnevale, Massimiliano De Lucia, Giuseppe Cifelli, Giuseppe Lembo

Research output: Contribution to journalArticle

Abstract

The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension.

Original languageEnglish
Article number13035
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Sep 27 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Carnevale, D., Perrotta, M., Pallante, F., Fardella, V., Iacobucci, R., Fardella, S., Carnevale, L., Carnevale, R., De Lucia, M., Cifelli, G., & Lembo, G. (2016). A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication. Nature Communications, 7, [13035]. https://doi.org/10.1038/ncomms13035