Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection

Fujiwara, S; Hoshizaki, Midori; Yu, I.; Lex, Dennis; Kuroda, Etsushi; Ishii, Ken J.; Magi, Shigeyuki; Okada, Mariko; Takao, H.; Gandou, Masahiro; Imai, Hideki; Hara, Ryujiro; Herzog, Herbert; Yoshimura, Akihiko; Okamura, Hitoshi; Penninger, Josef; Slutsky, Arthur S.; Uhlig, Stefan; Kuba, Keiji; Imai, Yumiko

doi:10.1038/s41564-018-0289-1

Cited by 15 publications

(13 citation statements)

References 47 publications

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“…57 Some of the effects of the sympathetic nervous system may be mediated by an increase release of not only catecholamines, but also neuropeptide Y (NPY), the release of which from monocytes also contributes to influenza-associated fatality. 58 In contrast, the activation of the parasympathetic nervous system following the vagal nerve release of acetylcholine, affords protection against some viral infections via the activation of the alpha 7 acetylcholine nicotinic receptor (α7nAChR), 59 including decreasing macrophage inflammatory responses. 60 It should be noted that the α7nAChR is intimately associated with melatonin, being positively regulated by pineal melatonin over the circadian rhythm, 61 whilst the impact of melatonin in preventing gut permeability under challenge is mediated by its induction of vagal nerve ACh release and subsequent α7nAChR activation.…”

Section: Gut Microbiomementioning

confidence: 99%

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Anderson¹,

Reíter

2020

Reviews in Medical Virology

183

173

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There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus-and cytokinestorm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.

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Section: Gut Microbiomementioning

confidence: 99%

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Anderson¹,

Reíter

2020

Reviews in Medical Virology

183

173

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“…However, based on the results obtained in the context of other viral infections, one may speculate that NPY could have a protective role during HSV-1 infection of the CNS, as such an effect has been reported in the context of retrovirus-induced neurological disease, which shares several traits with HSV-1 neuroinflammation, such as glial cell activation and the production of proinflammatory cytokines in the CNS ( 186 , 187 ). However, this factor may have detrimental effects during peripheral infections, as a recent study showed that NPY induced a worse course of influenza infection in mice when this neuropeptide was produced by immune cells in the lungs ( 188 ).…”

Section: Neuronal Signals Regulating the Immune System And Hsv-1 Infectionmentioning

confidence: 99%

Crosstalk Between Epithelial Cells, Neurons and Immune Mediators in HSV-1 Skin Infection

et al. 2021

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Herpes simplex virus type 1 (HSV-1) infection is highly prevalent in humans, with approximately two-thirds of the world population living with this virus. However, only a fraction of those carrying HSV-1, which elicits lifelong infections, are symptomatic. HSV-1 mainly causes lesions in the skin and mucosae but reaches the termini of sensory neurons innervating these tissues and travels in a retrograde manner to the neuron cell body where it establishes persistent infection and remains in a latent state until reactivated by different stimuli. When productive reactivations occur, the virus travels back along axons to the primary infection site, where new rounds of replication are initiated in the skin, in recurrent or secondary infections. During this process, new neuron infections occur. Noteworthy, the mechanisms underlying viral reactivations and the exit of latency are somewhat poorly understood and may be regulated by a crosstalk between the infected neurons and components of the immune system. Here, we review and discuss the immune responses that occur at the skin during primary and recurrent infections by HSV-1, as well as at the interphase of latently-infected neurons. Moreover, we discuss the implications of neuronal signals over the priming and migration of immune cells in the context of HSV-1 infection.

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“…Endothelial dysfunction can stimulate the secretion of NPY and promote leukocyte chemotaxis, thus expanding vascular inflammation (37, [105][106][107]. NPY also directly regulates inflammation in human ECs (108,109). In addition, inflammation stress plays a role in obesity-related cognitive impairment (110,111).…”

Section: Npy Nicotine and Oxidative Stressmentioning

confidence: 99%

Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis

Yanli

Wang

et al. 2021

Front. Cardiovasc. Med.

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Cardiovascular disease is the leading cause of death worldwide. Endothelial dysfunction of the arterial vasculature plays a pivotal role in cardiovascular pathogenesis. Nicotine-induced endothelial dysfunction substantially contributes to the development of arteriosclerotic cardiovascular disease. Nicotine promotes oxidative inflammation, thrombosis, pathological angiogenesis, and vasoconstriction, and induces insulin resistance. However, the exact mechanism through which nicotine induces endothelial dysfunction remains unclear. Neuropeptide Y (NPY) is widely distributed in the central nervous system and peripheral tissues, and it participates in the pathogenesis of atherosclerosis by regulating vasoconstriction, energy metabolism, local plaque inflammatory response, activation and aggregation of platelets, and stress and anxiety-related emotion. Nicotine can increase the expression of NPY, suggesting that NPY is involved in nicotine-induced endothelial dysfunction. Herein, we present an updated review of the possible mechanisms of nicotine-induced atherosclerosis, with a focus on endothelial cell dysfunction associated with nicotine and NPY.

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Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection

Cited by 15 publications

References 47 publications

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Melatonin: Roles in influenza, Covid‐19, and other viral infections

Crosstalk Between Epithelial Cells, Neurons and Immune Mediators in HSV-1 Skin Infection

Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis

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