Neuroimmune regulation of lung infection and inflammation

Abstract

The distal airway of the lung is innervated by vagus nerve. Upon stimulation, vagus nerve endings release acetylcholine or neuropeptides via C-fiber afferents to regulate lung infection and immunity. Vagal sensory nerve endings, brain integration center, acetylcholine, and α7 nicotinic acetylcholine receptor (nAChR) expressing cells are key components of pulmonary parasympathetic inflammatory reflex. Meanwhile, this local machinery synergizes with spleen (as a functional hub of cholinergic anti-inflammatory pathway) to finely tune recruitment of the splenic α7 nAChR+CD11b+ cells into the inflamed lungs during lung infection. Recent studies have showed that lung group 2 innate lymphoid cells (ILC2) express both α7 nAChR and neuropeptide receptors. Acetylcholine and neuropeptides can regulate ILC2 and reshape pulmonary infection and immunity. Among the airway epithelial cells, pulmonary neuroendocrine cells (PNECs) are rare cell population; however, these cells are innervated by sensory nerve endings and they could secrete neuropeptides that influence lung infection and immunity.

Non-invasive Auricular Vagus Nerve Stimulation as a Potential Treatment for Covid19-Originated Acute Respiratory Distress Syndrome

“…Our hypotheses on the therapeutic effects of VNS-induced parasympathetic activity are supported by a wide range of state-of-the-art clinical and experimental data: decrease of pro-inflammatory cytokines and modulation of lung injuries by activation of the anti-inflammatory pathways, improvement of pulmonary and cardiac functions by adjusting the sympatho-vagal imbalance, etc. (Dos Santos et al, 2011 ; Krzyzaniak et al, 2011 ; Kessler et al, 2012 ; Kox et al, 2012 ; Levy et al, 2012 ; Reys et al, 2013 ; Tarras et al, 2013 ; Shinlapawittayatorn et al, 2014 ; Akella and Deshpande, 2015 ; Chen et al, 2016 ; Stavrakis and Po, 2016 ; Liu et al, 2017 ; Huang et al, 2019 ).…”

“…Covid-19 patients present increased levels of IL-1, IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-17, GCSF, MCSF, IP-10, MCP-1, MIP-1α, HGF, IFN-γ, and TNF-α (Guo et al, 2020 ). Vagal afferents in the lungs detect inflammatory tissue-damaging stimuli (Carr and Undem, 2003 ), while VNS reduces the storm of pro-inflammatory cytokines through ChAP and HPAA activation, without leading to immunosuppression (Dos Santos et al, 2011 ; Krzyzaniak et al, 2011 ; Akella and Deshpande, 2015 ; Huang et al, 2019 ). Consequently, we expect VNS to reduce the severity of Covid-19 inflammation-related complications and fatalities while preventing strong and deteriorating immune responses.…”

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

“…The role of the nervous system in regulating the immune response in infection and inflammatory processes is known. 173 In the opposite direction, it has been described that mediators released from leukocyte populations can modulate the activity and prolongation of the adjacent nerve fibers and infiltrate to the tumor. 174,175 Inflammatory mediators lead to the activation of peripheral sensory fibers that, in addition to promoting pain, lead to the release of substance P, a neuropeptide that promotes tumor growth.…”

Dysfunction of the Autonomic Nervous System and Its Role in the Pathogenesis of Septic Critical Illness (Review)

“…With the development of inflammation, an afferent impulse is transmitted along the vagal nerve from the periphery to the brain stem. In the opposite direction, the vagal efferent pathway transmits signals to the spleen, liver, intestines, and other organs [8][9][10][11][12][13][14][15][16]. Stimulation of the efferent vagal nerve, as well as the use of cholinesterase blockers, results in accumulation of acetylcholine in these organs.…”