RT Journal Article SR Electronic T1 The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.20.463417 DO 10.1101/2021.10.20.463417 A1 Katayama, Pedro L. A1 Leirão, Isabela P. A1 Kanashiro, Alexandre A1 Luiz, João Paulo M. A1 Cunha, Fernando Q. A1 Navegantes, Luiz C. C. A1 Menani, Jose V. A1 Zoccal, Daniel B. A1 Colombari, Débora S. A. A1 Colombari, Eduardo YR 2021 UL http://biorxiv.org/content/early/2021/12/13/2021.10.20.463417.abstract AB Recent 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.Competing Interest StatementThe authors have declared no competing interest.