Aortic baroreceptor afferents as sensors for systemic inflammation

Area of Science:

• Cardiovascular Physiology
• Neuroimmunology
• Sensory Biology

Background:

• Neuroimmune communication regulates inflammation and cardiovascular homeostasis.
• Arterial baroreceptors, primarily mechanoreceptors, influence immune responses but their role in sensing systemic inflammation is unknown.
• The aortic depressor nerve (ADN) is a key component of baroreceptor function.

Purpose of the Study:

• To investigate the molecular and functional profile of the rat aortic depressor nerve (ADN) in response to lipopolysaccharide (LPS)-induced endotoxemia.
• To determine if arterial baroreceptors function as immunosensors.
• To characterize the neuroimmune axis involved in sensing systemic inflammation.

Main Methods:

• Gene expression analysis (RT-qPCR).
• Total protein quantification.
• Immunofluorescence assays.
• Electrophysiological recordings of ADN activity in rats.
• LPS-induced endotoxemia model.

Main Results:

• The rat ADN constitutively expresses innate immune signaling components (TLR4, MyD88, pNF-κB), indicating immunological vigilance.
• LPS administration upregulated inflammatory gene expression (NF-κB, IL-6, IL-1R type I) in the ADN and increased its electrical activity.
• Increased ADN nerve firing occurred during hypotension and the diastolic phase, independent of mechanosensory reflex.
• A coordinated neuroimmune sensory axis was identified involving the nodose ganglion and aortic arch.

Conclusions:

• Arterial baroreceptors function as integrative immunosensors, actively detecting and responding to systemic inflammation.
• A novel neuroimmune circuit links inflammation and the cardiovascular system.
• This neuroimmune circuit represents a potential therapeutic target for cardiovascular and inflammatory diseases.