Anatomical and clinical implications of vagal modulation of the spleen

Bassi, Gabriel Shimizu; Kanashiro, Alexandre; Coimbra, Norberto Cysne; Terrando, Niccolò; Maixner, William; Ulloa, Luis

doi:10.1016/j.neubiorev.2020.02.011

Cited by 53 publications

(40 citation statements)

References 128 publications

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“…On the other hand, an anti-inflammatory mechanism has been ascribed to the parasympathetic system which is proposed to monitor systemic inflammation through a reflex system and to activate a neuronal anti-inflammatory signal to prevent deleterious inflammation [81] . In contradistinction to SNS hyperactivation, which appears to be of particular significance for injury to the CV system [82] , inflammatory cytokines can activate the afferent sensory vagus nerve that transmits the information to the central nervous system which then can activate the efferent vagus nerve to control inflammation via acetylcholine, its principal neurotransmitter, and a nicotinic anti-inflammatory pathway and modulate the immune system by inhibiting the production of inflammatory cytokines in macrophages and the spleen [ 83 , 84 ]. In this context, diminished cardiac vagal activity, found in patients with pulmonary and cardiometabolic disease, has been shown to adversely affect patients with critical illness, such as COVID-19 infection [85] .…”

Section: Autonomic Imbalancementioning

confidence: 99%

COVID-19 infection and cardiac arrhythmias

Manolis¹,

Manolis

et al. 2020

Trends in Cardiovascular Medicine

112

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Highlights Serious cardiac arrhythmias may be the consequence of direct effects of COVID-19 infection, but also the outcome of the deleterious effects of systemic illness and the adverse proarrhythmic reactions to drugs employed in the treatment of this pandemic Drug combinations, especially of QT-prolonging agents, can lead to higher arrhythmogenicity, compared with single drug therapies Furthermore, critically ill COVID-19 patients often have comorbidities that can trigger life-threatening ventricular arrhythmias, while acute myocardial injury increases the prevalence of arrhythmias ECG and QTc monitoring and taking appropriate measures are of critical importance to prevent, detect and manage cardiac arrhythmias in COVID-19 patients Contactless monitoring and telemetry for inpatients, especially those admitted to the ICU, as well as for outpatients needing continued management, has recently been facilitated by implementing digital health monitoring tools

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Section: Autonomic Imbalancementioning

confidence: 99%

COVID-19 infection and cardiac arrhythmias

Manolis¹,

Manolis

et al. 2020

Trends in Cardiovascular Medicine

112

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“…The classical view of the ANS identifies its two main arms, the sympathetic and parasympathetic nervous systems, as key modulators of blood pressure, heart rate, vascular tone, and renal function ( Abboud, 1982 ). Yet one efferent arm of the ANS, directed to the spleen, has also been considered a critical modulator of immune responses ( Bassi et al., 2020 ; Chavan et al., 2017 ; Ordovas-Montanes et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Celiac Vagus Nerve Stimulation Recapitulates Angiotensin II-Induced Splenic Noradrenergic Activation, Driving Egress of CD8 Effector Cells

et al. 2020

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Summary Angiotensin II (AngII) is a peptide hormone that affects the cardiovascular system, not only through typical effects on the vasculature, kidneys, and heart, but also through less understood roles mediated by the brain and the immune system. Here, we address the hard-wired neural connections within the autonomic nervous system that modulate splenic immunity. Chronic AngII infusion triggers burst firing of the vagus nerve celiac efferent, an effect correlated with noradrenergic activation in the spleen and T cell egress. Bioelectronic stimulation of the celiac vagus nerve, in the absence of other challenges and independently from afferent signals to the brain, evokes the noradrenergic splenic pathway to promote release of a growth factor mediating neuroimmune crosstalk, placental growth factor (PlGF), and egress of CD8 effector T cells. Our findings also indicate that the neuroimmune interface mediated by PlGF and necessary for transducing the neural signal into an effective immune response is dependent on α-adrenergic receptor signaling.

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“…In the white pulp, a highly-organized lymphoid structure is responsible for the local and systemic regulation of immunity 10 . Accumulating evidence suggests that an intricate communication exists between the PNS and the spleen, and that this crosstalk might play an essential role in the regulation of the immune response 9,[11][12][13][14][15][16][17] . Therefore, an understanding of the splenic innervation by both autonomic (efferent) and sensory (afferent) fibers is crucial for a better appreciation of the response of the spleen to immune challenge and tissue injury.…”

mentioning

confidence: 99%

“…Sympathetic norepinephrine fibers enter the spleen via the splenic nerve, and much of the network is closely associated with the splenic artery and its branches into the spleen [18][19][20] . These sympathetic nerve fibers might have close associations with lymphocytes, macrophages, and DCs [14][15][16] . In addition, sensory innervation of the spleen has also been reported 11,13 .…”

mentioning

confidence: 99%

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

Al-Shalan

Shi

et al. 2020

Sci Rep

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The central nervous system regulates the immune system through the secretion of hormones from the pituitary gland and other endocrine organs, while the peripheral nervous system (PNS) communicates with the immune system through local nerve-immune cell interactions, including sympathetic/parasympathetic (efferent) and sensory (afferent) innervation to lymphoid tissue/organs. However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerveimmune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1 + and F4/80 +), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular-and humoral-mediated immune responses in healthy and infectious/noninfectious states. The human nervous system includes the central nervous system (CNS; containing the brain and spinal cord) and the peripheral nervous system (PNS; containing the sensory (somatic sensory and visceral sensory) and motor (somatic motor divisions and the autonomic nervous system (ANS; including sympathetic, parasympathetic, and enteric components))) 1. Recent studies have demonstrated that bi-directional communication/interaction between the nervous system and the immune system plays a crucial role in the host's responses to pathogen invasion, tissue injury, and other homeostatic dangers/threats 1-5. The functional organization of the neural control of the immune system is based on principles of reflex regulation 6. For example, the immune system is regulated by the CNS through the secretion of hormones from the pituitary and other neuroendocrine/endocrine organs 7,8 and by the PNS through local nerve (fiber)-immune cell interactions. The PNS can regulate the development, deployment, and homeostatic regulation of the immune system 3. This type of local neuroimmune interaction involves the "hardwiring" of sympathetic/parasympathetic (efferent) and visceral sensory (afferent) nerves to primary and secondary lymphoid tissue/organs 4-6. Neurotransmitters (e.g., acetylcholine, norepinephrine, and histamine) and neuropeptides (e.g., vasoactive intestinal peptide and substance P) released from nerve terminals (or even from the immune cells) might modulate the immune response in homeostasis and diseases 9. Cytokines and other immunologic factors synthesized a...

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Anatomical and clinical implications of vagal modulation of the spleen

Cited by 53 publications

References 128 publications

COVID-19 infection and cardiac arrhythmias

COVID-19 infection and cardiac arrhythmias

Celiac Vagus Nerve Stimulation Recapitulates Angiotensin II-Induced Splenic Noradrenergic Activation, Driving Egress of CD8 Effector Cells

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

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