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Annual Review of Immunology Apr 2018The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates... (Review)
Review
The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.
Topics: Animals; Biomarkers; Disease Susceptibility; Humans; Immunity; Nervous System; Nervous System Physiological Phenomena; Neuroimmunomodulation; Signal Transduction; Translational Research, Biomedical
PubMed: 29677475
DOI: 10.1146/annurev-immunol-042617-053158 -
Annual Review of Neuroscience Jul 2022Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously... (Review)
Review
Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.
Topics: Immune System; Neuroimmunomodulation; Peripheral Nervous System
PubMed: 35363534
DOI: 10.1146/annurev-neuro-111020-105359 -
Nature Reviews. Neuroscience Mar 2022Bidirectional communication between the peripheral nervous system (PNS) and the immune system is a crucial part of an effective but balanced mammalian response to... (Review)
Review
Bidirectional communication between the peripheral nervous system (PNS) and the immune system is a crucial part of an effective but balanced mammalian response to invading pathogens, tissue damage and inflammatory stimuli. Here, we review how somatosensory and autonomic neurons regulate immune cellular responses at barrier tissues and in peripheral organs. Immune cells express receptors for neuronal mediators, including neuropeptides and neurotransmitters, allowing neurons to influence their function in acute and chronic inflammatory diseases. Distinct subsets of peripheral sensory, sympathetic, parasympathetic and enteric neurons are able to signal to innate and adaptive immune cells to modulate their cellular functions. In this Review, we highlight recent studies defining the molecular mechanisms by which neuroimmune signalling mediates tissue homeostasis and pathology. Understanding the neural circuitry that regulates immune responses can offer novel targets for the treatment of a wide array of diseases.
Topics: Animals; Humans; Immune System; Immunity; Mammals; Neuroimmunomodulation; Neuropeptides; Peripheral Nervous System
PubMed: 34997214
DOI: 10.1038/s41583-021-00555-4 -
Journal of Neuroinflammation Jan 2020Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients.... (Review)
Review
Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.
Topics: Animals; Humans; Immune Tolerance; Neuroimmunomodulation; Sepsis; Sepsis-Associated Encephalopathy
PubMed: 31924221
DOI: 10.1186/s12974-020-1701-3 -
British Journal of Anaesthesia Nov 2019The relationship between gut microbiota and neurological diseases, including chronic pain, has received increasing attention. The gut microbiome is a crucial modulator... (Review)
Review
The relationship between gut microbiota and neurological diseases, including chronic pain, has received increasing attention. The gut microbiome is a crucial modulator of visceral pain, whereas recent evidence suggests that gut microbiota may also play a critical role in many other types of chronic pain, including inflammatory pain, headache, neuropathic pain, and opioid tolerance. We present a narrative review of the current understanding on the role of gut microbiota in pain regulation and discuss the possibility of targeting gut microbiota for the management of chronic pain. Numerous signalling molecules derived from gut microbiota, such as by-products of microbiota, metabolites, neurotransmitters, and neuromodulators, act on their receptors and remarkably regulate the peripheral and central sensitisation, which in turn mediate the development of chronic pain. Gut microbiota-derived mediators serve as critical modulators for the induction of peripheral sensitisation, directly or indirectly regulating the excitability of primary nociceptive neurones. In the central nervous system, gut microbiota-derived mediators may regulate neuroinflammation, which involves the activation of cells in the blood-brain barrier, microglia, and infiltrating immune cells, to modulate induction and maintenance of central sensitisation. Thus, we propose that gut microbiota regulates pain in the peripheral and central nervous system, and targeting gut microbiota by diet and pharmabiotic intervention may represent a new therapeutic strategy for the management of chronic pain.
Topics: Blood-Brain Barrier; Chronic Pain; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Inflammation; Neuroimmunomodulation; Pain Management; Visceral Pain
PubMed: 31551115
DOI: 10.1016/j.bja.2019.07.026 -
Nature Dec 2022The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the... (Review)
Review
The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the central nervous system as central sites of neuro-immune interactions. Although the nervous and immune systems both function to maintain homeostasis, under rare circumstances, they can develop pathological interactions that lead to neurological or psychiatric diseases. Here we discuss recent findings that dissect the key anatomical, cellular and molecular mechanisms that enable neuro-immune responses at the borders of the brain and spinal cord and the implications of these interactions for diseases of the central nervous system.
Topics: Brain; Immune System; Neuroimmunomodulation; Spinal Cord; Humans; Nervous System Diseases
PubMed: 36517712
DOI: 10.1038/s41586-022-05474-7 -
Frontiers in Immunology 2022Progress in neuroimmunology established that the nervous and the immune systems are two functionally related physiological systems. Unique sensory and immune receptors... (Review)
Review
Progress in neuroimmunology established that the nervous and the immune systems are two functionally related physiological systems. Unique sensory and immune receptors enable them to control interactions of the organism with the inner and the outer worlds. Both systems undergo an experience-driven selection process during their ontogeny. They share the same mediators/neurotransmitters and use synapses for intercellular communication. They keep a memory of previous experiences. Immune cells can affect nervous cells, nervous cells can affect immune cells, and they regulate each other. I however argue that the two systems differ by three major points: 1) Unlike the nervous system, the immune system has a loose anatomical structure, in which molecular and cellular events mostly occur at random; 2) The immune system can respond to the whereas the nervous system can respond to ; 3) Responses of the immune system act both on the organism and on the stimulus that triggered the response, whereas responses of the nervous system act on the organism only. The nervous and the immune systems therefore appear as two complementary that closely work together, and whose reactivities are well-suited to deal with physical and biological stimuli, respectively. Its ability both to adapt the organism to the living world and to adapt the living world to the organism endows the immune system with powerful adaptive properties that enable the organism to live in peace with itself and with other living beings, whether pathogens or commensals.
Topics: Cell Communication; Immune System; Nervous System; Neuroimmunomodulation; Neurotransmitter Agents
PubMed: 36177051
DOI: 10.3389/fimmu.2022.984678 -
International Journal of Molecular... Sep 2020One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a... (Review)
Review
One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the origin of signals with a proinflammatory position that can boost the cells in the brain and promote the penetration of numerous inflammatory cytotypes (various subtypes of T cells, monocytes/macrophages, neutrophils, and different inflammatory cells) within the area affected by ischemia; this process is responsible for further ischemic damage of the brain. This inflammatory process seems to involve both the cerebral tissue and the whole organism in cardioembolic stroke, the stroke subtype that is associated with more severe brain damage and a consequent worse outcome (more disability, higher mortality). In this review, the authors want to present an overview of the present learning of the mechanisms of inflammation that takes place in the cerebral tissue and the role of the immune system involved in ischemic stroke, focusing on cardioembolic stroke and its potential treatment strategies.
Topics: Animals; Brain; Brain Ischemia; Cytokines; Embolic Stroke; Humans; Inflammation; Ischemic Stroke; Neuroimmunomodulation; Stroke
PubMed: 32899616
DOI: 10.3390/ijms21186454 -
International Journal of Molecular... Apr 2021With the world's population ageing, the incidence of Parkinson's disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent... (Review)
Review
With the world's population ageing, the incidence of Parkinson's disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.
Topics: Animals; Brain; Cytokines; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Humans; Inflammation; Microglia; Nerve Degeneration; Neuroimmunomodulation; Neurons; Neuroprotection; Oxidative Stress; Parkinson Disease; alpha-Synuclein
PubMed: 33925154
DOI: 10.3390/ijms22094676 -
Cell Reports. Medicine Jul 2022The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune... (Review)
Review
The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune responses. Signals communicated via the vagus and splenic nerves use acetylcholine, produced by Choline acetyltransferase (ChAT)+ T cells, to downregulate the inflammatory actions of macrophages expressing α7 nicotinic receptors. Pre-clinical studies using transgenic animals, cholinergic agonists, vagotomy, and vagus nerve stimulation have demonstrated this pathway's role and therapeutic potential in numerous inflammatory diseases. In this review, we summarize what is understood about the inflammatory reflex. We also demonstrate how pre-clinical findings are being translated into promising clinical trials, and we draw particular attention to innovative bioelectronic methods of harnessing the cholinergic anti-inflammatory pathway for clinical use.
Topics: Animals; Neuroimmunomodulation; Reflex; Vagus Nerve; Vagus Nerve Stimulation; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35858588
DOI: 10.1016/j.xcrm.2022.100696