The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex

• DOI: 10.1016/j.bbi.2022.03.014
• Publication Date: 2022-03-23T16:41:27Z
• Authors: Pedro L. Katayama; Isabela P. Leirão; Alexandre Kanashiro; João P.M. Luiz; Fernando Q. Cunha; Luiz C.C. Navegantes; Jose V. Menani; Daniel B. Zoccal; Débora S.A. Colom...; Eduardo Colombari
• Keywords: Inflammation; Neuroimmune interactions; 0301 basic medicine; Carotid Body; Medulla Oblongata; 0303 health sciences; Sympathetic Nervous System; Neuroimmunomodulation; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents; Neural circuits; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Carotid body; Sympathetic nervous system; Reflex; Solitary Nucleus; Animals

AbstractRecent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sympathetic denervation. Collectively, our findings indicate that the carotid body detects circulating TNF-α to activate a counteracting sympathetic anti-inflammatory mechanism.