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The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex

Pedro L. Katayama, Isabela P. Leirão, Alexandre Kanashiro, João Paulo M. Luiz, Fernando Q. Cunha, Luiz C. C. Navegantes, Jose V. Menani, Daniel B. Zoccal, Débora S. A. Colombari, Eduardo Colombari
doi: https://doi.org/10.1101/2021.10.20.463417
Pedro L. Katayama
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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  • For correspondence: katayamapl@gmail.com eduardo.colombari@unesp.br
Isabela P. Leirão
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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Alexandre Kanashiro
2Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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João Paulo M. Luiz
3Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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Fernando Q. Cunha
3Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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Luiz C. C. Navegantes
4Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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Jose V. Menani
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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Daniel B. Zoccal
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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Débora S. A. Colombari
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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Eduardo Colombari
1Department of Physiology and Pathology, School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil
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  • For correspondence: katayamapl@gmail.com eduardo.colombari@unesp.br
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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 Statement

The authors have declared no competing interest.

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Posted December 13, 2021.
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The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex
Pedro L. Katayama, Isabela P. Leirão, Alexandre Kanashiro, João Paulo M. Luiz, Fernando Q. Cunha, Luiz C. C. Navegantes, Jose V. Menani, Daniel B. Zoccal, Débora S. A. Colombari, Eduardo Colombari
bioRxiv 2021.10.20.463417; doi: https://doi.org/10.1101/2021.10.20.463417
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The Carotid Body Detects Circulating Tumor Necrosis Factor-Alpha to Activate a Sympathetic Anti-Inflammatory Reflex
Pedro L. Katayama, Isabela P. Leirão, Alexandre Kanashiro, João Paulo M. Luiz, Fernando Q. Cunha, Luiz C. C. Navegantes, Jose V. Menani, Daniel B. Zoccal, Débora S. A. Colombari, Eduardo Colombari
bioRxiv 2021.10.20.463417; doi: https://doi.org/10.1101/2021.10.20.463417

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