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 and Giuseppe Lembo ()
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Daniela Carnevale: IRCCS Neuromed
Marialuisa Perrotta: IRCCS Neuromed
Fabio Pallante: IRCCS Neuromed
Valentina Fardella: IRCCS Neuromed
Roberta Iacobucci: IRCCS Neuromed
Stefania Fardella: IRCCS Neuromed
Lorenzo Carnevale: IRCCS Neuromed
Raimondo Carnevale: IRCCS Neuromed
Massimiliano De Lucia: IRCCS Neuromed
Giuseppe Cifelli: IRCCS Neuromed
Giuseppe Lembo: IRCCS Neuromed

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13035

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