Neuro-Immune Interactions at Barrier Surfaces

Veiga-Fernandes, Henrique; Mucida, Daniel

doi:10.1016/j.cell.2016.04.041

Cited by 223 publications

(183 citation statements)

References 122 publications

(159 reference statements)

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“…Increasing evidence indicates that the metazoan nervous system, which responds to stimuli originating from both the internal and the external environment, functions as a modulatory apparatus that controls not only microbial killing pathways but also cellular homeostatic mechanisms [3–5]. Here, we report that dopamine signaling controls innate immune responses through a D1-like dopamine receptor, DOP-4, in Caenorhabditis elegans .…”

mentioning

confidence: 86%

Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner

Cao

Aballay

2016

Current Biology

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SUMMARY The innate immune system is the frontline of host defense against microbial infections, but its rapid and uncontrolled activation elicits microbicidal mechanisms that have deleterious effects [1, 2]. Increasing evidence indicates that the metazoan nervous system, which responds to stimuli originating from both the internal and the external environment, functions as a modulatory apparatus that controls not only microbial killing pathways but also cellular homeostatic mechanisms [3–5]. Here, we report that dopamine signaling controls innate immune responses through a D1-like dopamine receptor, DOP-4, in Caenorhabditis elegans. Chlorpromazine inhibition of DOP-4 in the nervous system activates a microbicidal PMK-1/p38 mitogen-activated protein kinase signaling pathway that enhances host resistance against bacterial infections. The immune inhibitory function of dopamine originates in CEP neurons and requires active DOP-4 in downstream ASG neurons. Our findings indicate that dopamine signaling from the nervous system controls immunity in a cell non-autonomous manner and identifies the dopaminergic system as a potential therapeutic target for not only infectious diseases but also a range of conditions that arise as a consequence of malfunctioning immune responses.

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mentioning

confidence: 86%

Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner

Cao

Aballay

2016

Current Biology

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“…Regulation of the immune system and inflammation by the peripheral nervous system has been studied for a long time, and is beginning to recapture a great amount of attention [53, 75]. In pharmacologically induced murine dermatitis that resembles human psoriasis, nociceptive sensory neurons were reported to promote the production of proinflammatory cytokine IL-23 by dermal dendritic cells, and this study visualized contacts of dendritic cells with sensory nerve fibers by intravital microscopy [58].…”

Section: Imaging Of Interactions Between Immune Cells and Non-immune mentioning

confidence: 99%

In vivo multiphoton imaging of immune cell dynamics

Okada

Takahashi

Ishida

et al. 2016

Pflugers Arch - Eur J Physiol

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Multiphoton imaging has been utilized to analyze in vivo immune cell dynamics over the last 15 years. Particularly, it has deepened the understanding of how immune responses are organized by immune cell migration and interactions. In this review, we first describe the following technical advances in recent imaging studies that contributed to the new findings on the regulation of immune responses and inflammation. Improved multicolor imaging of immune cell behavior has revealed that their interactions are spatiotemporally coordinated to achieve efficient and long-term immunity. The use of photoactivatable and photoconvertible fluorescent proteins has increased duration and volume of cell tracking, even enabling the analysis of inter-organ migration of immune cells. In addition, visualization of immune cell activation using biosensors for intracellular calcium concentration and signaling molecule activities has started to give further mechanistic insights. Then, we also introduce recent imaging analyses of interactions between immune cells and non-immune cells including endothelial, fibroblastic, epithelial, and nerve cells. It is argued that future imaging studies that apply updated technical advances to analyze interactions between immune cells and non-immune cells will be important for thorough physiological understanding of the immune system.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-016-1882-x) contains supplementary material, which is available to authorized users.

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“…The nervous and immune systems work in concert to sense potential pathogens and provide host-protective responses (Ordovas-Montanes et al, 2015; Veiga-Fernandes and Mucida, 2016). Emerging evidence has demonstrated extensive crosstalk between these systems at multiple barrier surfaces including the gut (Gabanyi et al, 2016), lung (Talbot et al, 2015), and skin (Kashem et al, 2015; Riol-Blanco et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Oetjen

Mack

Feng

et al. 2017

Cell

798

786

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SUMMARY Mammals have evolved neurophysiologic reflexes such as coughing and scratching to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases such as asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.

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Neuro-Immune Interactions at Barrier Surfaces

Cited by 223 publications

References 122 publications

Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner

Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner

In vivo multiphoton imaging of immune cell dynamics

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

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