@article {Katayama2021.10.20.463417, author = {Pedro L. Katayama and Isabela P. Leir{\~a}o and Alexandre Kanashiro and Jo{\~a}o Paulo M. Luiz and Fernando Q. Cunha and Luiz C. C. Navegantes and Jose V. Menani and Daniel B. Zoccal and D{\'e}bora S. A. Colombari and Eduardo Colombari}, title = {The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex}, elocation-id = {2021.10.20.463417}, year = {2021}, doi = {10.1101/2021.10.20.463417}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2021/10/21/2021.10.20.463417}, eprint = {https://www.biorxiv.org/content/early/2021/10/21/2021.10.20.463417.full.pdf}, journal = {bioRxiv} }