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Arterial baroreceptors are typically defined as mechanoreceptors essential for arterial pressure homeostasis and have been associated with modulation of the immune response. However, their role in sensing systemic inflammation remains unknown. Here, we establish the molecular profile of the rat aortic depressor nerve (ADN) as an immune-competent tissue and investigate its response to lipopolysaccharide (LPS)-induced endotoxemia. Using analysis of gene expression, total protein quantification, and immunofluorescence assay, we demonstrate that the ADN, from male Sprague\u2013Dawley rats (7\u20138\u00a0weeks old), constitutively expresses key components for innate immune signalling, including Toll-like receptor 4 (TLR4), MyD88, and phosphorylated NF-\u03baB, indicating a state of constant immunological vigilance. LPS administration induced an inflammatory response within the ADN, upregulating gene expression of NF-\u03baB, interleukin-6, and type I interleukin 1 receptor, and it also\u00a0increased the ADN electrical activity. Notably, the increase in nerve firing occurred while the animals were experiencing systemic hypotension and also during the diastolic phase, indicating that this response is not from the mechanosensory reflex. Furthermore, we characterized the progression of this immune response in the nodose ganglion and aortic arch, identifying a coordinated neuroimmune sensory axis. These findings reposition arterial baroreceptors from purely mechanoreceptors to integrative immunosensors that actively detect and respond to systemic inflammation. This novel neuroimmune circuit represents a critical link between inflammation and cardiovascular system, offering a novel therapeutic target for treating cardiovascular and inflammatory conditions.<\/jats:p>","DOI":"10.1007\/s00395-026-01188-3","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:40:04Z","timestamp":1781282404000},"page":"755-773","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aortic baroreceptor afferents as sensors for systemic inflammation"],"prefix":"10.1007","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-1319","authenticated-orcid":false,"given":"Fernanda","family":"Brognara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaci Airton","family":"Castania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirele Resende","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Teles","family":"de Oliveira Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio Cesar","family":"Salgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita de Cassia","family":"Tostes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Penteado Martins","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian Francis Richmond","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelin Capellari","family":"C\u00e1rnio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"1188_CR1","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nri1391","volume":"4","author":"S Akira","year":"2004","unstructured":"Akira S, Takeda K (2004) Toll-like receptor signalling. 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