Gut Microbiota as a Mediator of Host Neuro-Immune Interactions: Implications in Neuroinflammatory Disorders.

The dynamic population of microbes that reside in the gastrointestinal tract plays a pivotal role in orchestrating several aspects of host physiology and health, including but not limited to nutrient extraction and metabolism, as well as the regulation of intestinal epithelial barrier integrity. Gut microbes interact with the host in a bi-directional manner as the microbiota can support the development and education of the innate and adaptive immune systems, thereby conferring protection against pathogens and harmful stimuli while training the host to maintain a homeostatic tolerance towards commensal symbiotics. Recent advances in the field have highlighted the importance of the host-microbiota relationship in neurodevelopment and behaviour, with relevant implications for the onset and progression of brain disorders of inflammatory origin. Microbial modulation of brain function is achieved throughout complex neuro-immune-endocrine pathways of the microbiome-gut-brain axis. Changes in the composition of the gut microbiota or perturbation in microbial-derived metabolites and neuroactive compounds are sensed by the afferent branches of the sympathetic and vagal innervation and transmitted to the central nervous system, which in turn produces behavioural responses. Here, we focus on how the crosstalk between the gut microbiota and the immune system modulates the development and function of the peripheral and central nervous systems. Specific attention is afforded to the involvement of host-microbe neuroimmune interactions in the pathogenesis of neuro-psychiatric and neuroinflammatory disorders such as autism spectrum disorders, anxiety, and depression, as well as Parkinson's and Alzheimer's diseases.

Anatomy and development of the human taste system.

The sense of taste relies on well-defined neuroanatomical structures, namely, the taste buds and afferent nerve fibers. Taste buds are clusters of 50-100 neuroepithelial cells located throughout the oral cavity, including the epiglottis and larynx. They are responsible for the initial transduction process that ultimately results in the perception of bitter, sour, salty, sweet, and umami (savory) sensations. They service as the initial sentinel for a sensory system critical in evolution for distinguishing "dangerous" food components, often perceived as bitter or unpleasant, from "useful" ones, often perceived as pleasant, salty, or sweet. This chapter describes the anatomy and development of the human peripheral taste system and provides historical context for what is presently known about this element of this important sensory system. Its main focus is on the fundamental question of how tastants are perceived-a question that has been of philosophical and scientific interest for more than two millennia. Descriptions of lingual and extralingual taste buds, their blood and nerve supplies, and the associated salivary glands are provided, including details of their microstructure and transduction mechanisms.

When an octopus has MS: Application of neurophysiology and immunology of octopuses for multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disease which can cause different symptoms due to the involvement of different regions of the central nervous system (CNS). Although this disease is characterized by the demyelination process, the most important feature of the disease is its degenerative nature. This nature is clinically manifested as progressive symptoms, especially in patients' walking, which can even lead to complete debilitation. Therefore, finding a treatment to prevent the degenerative processes is one of the most important goals in MS studies. To better understand the process and the effect of drugs, scientists use animal models which mostly consisting of mouse, rat, and monkey. In evolutionary terms, octopuses belong to the invertebrates which have many substantial differences with vertebrates. One of these differences is related to the nervous system of these organisms, which is divided into central and peripheral parts. The difference lies in the fact that the main volume of this system expands in the limbs of these organisms instead of their brain. This offers a kind of freedom of action and processing strength in the octopus limbs. Also, the brain of these organisms follows a non-somatotopic model. Although the complex actions of this organism are stimulated by the brain, in contrast to the human brain, this activity is not related to a specific region of the brain; rather the entire brain area of the octopus is activated during a process. Indeed, the brain mapping or the topological perception of a particular action, such as moving the limbs, reflects itself in how that activity is distributed in the octopus brain neurons. Accordingly, various actions are known with varying degrees of activity of neurons in the brain of octopus. Another important feature of octopuses is their ability to regenerate defective tissues including the central and peripheral nervous system. These characteristics raise the question of what features can an octopus show when it is used as an organism to create experimental autoimmune encephalomyelitis (EAE). Can the immune system damage of the octopus brain cause a regeneration process? Will the autonomy of the organs reduce the severity of the symptoms? This article seeks to provide evidence to prove that use of octopuses as laboratory samples for generation of EAE may open up new approaches for researchers to better approach MS.

Immune-Neuro-Endocrine Reflexes, Circuits, and Networks: Physiologic and Evolutionary Implications.

The existence of a network of interactions between the immune and nervous systems that influences host defenses and brain functions is now well-established. Here we discuss how immune and classical neuro/sensorial signals are processed in the brain and how neuro-endocrine immunoregulatory and behavioral responses are integrated. Considering the ability of brain cells to produce cytokines, originally described as immune cell products, we propose that the tripartite synapse plays a central role in the integration of neuro-endocrine-immune interactions. We also propose that the immune-neuro-endocrine responses that influence the course of transmissible and other diseases predisposing to infections can be relevant for evolution, either by restoring health or by mediating an active process of negative selection.

Neural regulation of immunity: molecular mechanisms and clinical translation.

Studies bridging neuroscience and immunology have identified neural pathways that regulate immunity and inflammation. Recent research using methodological advances in molecular genetics has improved our understanding of the neural control of immunity. Here we outline mechanistic insights, focusing on translational relevance and conceptual developments. We also summarize findings from recent clinical studies of bioelectronic neuromodulation in inflammatory and autoimmune diseases.

Stress, asthma, and respiratory infections: pathways involving airway immunology and microbial endocrinology.

Stress and infections have long been independently associated with asthma pathogenesis and exacerbation. Prior research has focused on the effect of psychological stress on Th cells with particular relevance to atopic asthma. In this review, we propose new perspectives that integrate the role of infection in the relationship between psychological stress and asthma. We highlight the essential role of the mucosal epithelia of the airways in understanding the interaction between infections and the stress-asthma relationship. In addition, we review findings suggesting that psychological stress not only modulates immune processes, but also the pathogenic qualities of bacteria, with implications for the pathogenesis and exacerbation asthma.

New insights on ctenophore neural anatomy: immunofluorescence study in Pleurobrachia pileus (Müller, 1776).

Ctenophores are non-bilaterian animals sharing with cnidarians and bilaterians the presence of sensory receptors, nerve cells, and synapses, absent in placozoans and sponges. Although recent immunofluorescence studies have renewed our knowledge of cnidarian neuro-anatomy, ctenophores have been much less investigated despite their importance to understanding the origin and early evolution of the nervous system. In this study, the neuro-anatomy of the ctenophore Pleurobrachia pileus (Müller, 1776) was explored by whole-mount fluorescent antibody staining using antibodies against tyrosylated -tubulin, FMRFamide, and vasopressin. We describe the morphology of nerve nets and their local specializations, and the organization of the aboral neuro-sensory complex comprising the apical organ and polar fields. Two distinct nerve nets are distinguished: a mesogleal nerve net, loosely organized throughout body mesoglea, and a much more compact "nerve net" with polygonal meshes in the ectodermal epithelium. The latter is organized as a plexus of short nerve cords. This epithelial nervous system contains distinct sub-populations of dispersed FMRFamide and vasopressin immunoreactive nerve cells. In the aboral neuro-sensory complex, our most significant observations include specialized nerve nets underlying the apical organ and polar fields, a tangential bundle of actin-rich fibers (interpreted as a muscle) within the polar fields, and distinct groups of neurons labeled by anti-FMRFamide and anti-vasopressin antibodies, within the apical organ floor. These results are discussed in a comparative perspective.

Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S) mutant gene: identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration.

Wallerian degeneration (WD) involves the fragmentation of axonal segments disconnected from their cell bodies, segmentation of the myelin sheath, and removal of debris by Schwann cells and immune cells. The removal and downregulation of myelin-associated inhibitors of axonal regeneration and synthesis of growth factors by these two cell types are critical responses to successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve of mice carrying the Wallerian degeneration slow (Wld(S)) mutant gene, a gene that confers axonal protection in the distal stump after injury, therefore causing significant delays in WD, neuroinflammation, and axonal regeneration. Of the thousands of genes analyzed by microarray, 719 transcripts were differentially expressed between Wld(S) and wild-type (wt) mice. Notably, the Nmnat1, a transcript contained within the sequence of the Wld(S) gene, was upregulated by five to eightfold in the sciatic nerve of naive Wld(S) mice compared with wt. The injured sciatic nerve of wt could be further distinguished from the one of Wld(S) mice by the preferential upregulation of genes involved in axonal processes and plasticity (Chl1, Epha5, Gadd45b, Jun, Nav2, Nptx1, Nrcam, Ntm, Sema4f), inflammation and immunity (Arg1, Lgals3, Megf10, Panx1), growth factors/cytokines and their receptors (Clcf1, Fgf5, Gdnf, Gfrα1, Il7r, Lif, Ngfr/p75(NTR), Shh), and cell adhesion and extracellular matrix (Adam8, Gpc1, Mmp9, Tnc). These results will help understand how the nervous and immune systems interact to modulate nerve repair, and identify the molecules that drive these responses.

Neuroimmunology of the circadian clock.

Circadian timekeeping is a ubiquitous feature of all eukaryotes which allows for the imposition of a biologically appropriate temporal architecture on an animal's physiology, behavior and metabolism. There is growing evidence that in mammals the processes of circadian timing are under the influence of the immune system. Such a role for the neuroimmune regulation of the circadian clock has inferences for phenomena such as sickness behavior. Conversely, there is also accumulating evidence for a circadian influence on immune function, raising the likelihood that there is a bidirectional communication between the circadian and immune systems. In this review, we examine the evidence for these interactions, including circadian rhythmicity in models of disease and immune challenge, distribution of cytokines and their receptors in the suprachiasmatic nucleus of the hypothalamus, the site of the master circadian pacemaker, and the evidence for endogenous circadian timekeeping in immune cells.

The alchemy of immune privilege explored from a neuroimmunological perspective.

The term 'immune privilege' (IP) generally describes the protection of vital structures, such as the brain, the eye, or the pregnant uterus, from the potentially damaging effects of an inflammatory immune response. Initially, barriers physically camouflaging such organs were thought to shield autoantigens from immune recognition and inflammation. This simplistic concept gave way to a much more complex understanding of IP, which reflects an entire network of interacting immunoregulatory processes and immunosuppressive microenvironments. Also, the number of organs and tissues that enjoy relative IP has grown considerably. This is not surprising since many different organs are constantly exposed to major, potentially damaging inflammatory events, for example, skin, gut, or lung-without evidence for excessive inflammation under physiological conditions. Focusing on fetotrophoblast IP as well as on hair-follicle-associated IP (an underappreciated, yet biologically fascinating, clinically important IP model), we summarize here key regulatory cues that operate in immunoprivileged tissues. Proposing novel concepts of how IP may collapse, for example, by exposure to psychosocial, stress-associated inflammation, we develop related strategies for how IP may be manipulated clinically so as to achieve IP protection and restoration.