There are numerous levels of overlap between the nervous and immune systems. This includes shared production of effector molecules and shared expression of receptors, allowing nerve cells to respond to cytokines produced by immune cells, and allowing immune cells to directly sense and respond to neurotransmitters. Both of these systems facilitate the protection of the organism, the nervous system by removal and avoidance of noxious triggers, and the immune system through the targeting and elimination of invading pathogens. Despite the high degree of interaction between these two systems, the investigation of how these disseminated organs interact and influence one another is only beginning to be explored.
Recent discoveries have highlighted this interaction in numerous organ systems, including the skin, mucosal barrier tissues, and secondary lymphoid organs. In the skin, researchers have found substance P and calcitonin gene-related peptide (CGRP) released from sensory neurons influences the type of immune response induced locally and can improve immune resistance by activating innate-like cell types such as gd T cells and Langerhans cells. In some cases, pathogens have hijacked the sensory nervous system in order to evade immune responses and facilitate their persistence in their host. For example, streptococcus pyogenes activates sensory neurons to induce the release of CGRP, which inhibits the recruitment of neutrophils and promotes the survival of the bacteria.
Communication between immune cells and the nervous system is bidirectional; sensory nerves express receptors for inflammatory cytokines, including IL-1b and TNFa, released from the immune system, allowing the nervous system to survey and monitor ongoing immune responses. Signaling by these proinflammatory cytokines sensitizes these sensory nerve fibers and can lead to chronic pain, Furthermore, there is increasing evidence that T cells participate in sensory nerve activation and function. In rodent models of chronic pain after nerve injury, loss of T cells reduced hypersensitivity after nerve injury.
In addition to receptors for substance P and CGRP, both adaptive and innate immune cells also express receptors for catecholamines and acetylcholine released from the sympathetic and parasympathetic arms of the nervous system, respectively. The actions of these neurotransmitters on immune function are complex and often contradictory, likely due to the wide diversity of receptors expressed by immune cells. In addition to neuronally-derived catecholamines and acetylcholine, immune cells are also capable of producing these neurotransmitters during the course of an immune response. In preclinical models of autoimmune arthritis, catecholamine signaling potentiates disease development early in the response and ameliorates disease symptoms later, highlighting the complexity of understanding how the immune system integrates with the sympathetic nervous system. Likewise, signaling by acetylcholine through the a7 nicotinic acetylcholine receptor inhibits macrophage activation and is protective from lethal inflammation associated with sepsis. However, during disseminated viral infection, acetylcholine produced by T cells is required for efficient migration of these cells into infected tissues, and the elimination of the virus.
In this Research Topic, we will explore three broad themes to better understand the intersection of immunity and neuronal signaling. First, how nervous system signaling can activate and inhibit immune function. Second, how immune cells, in turn, influence neuronal activation and signaling, and third, how pathogens manipulate neuronal signaling to evade immune-mediated elimination.
We welcome authors to submit Original Research, Review, Case Report, Clinical Trial, and Methods article types focusing on, but not limited to:
1. Neurotransmitter-mediated activation or inhibition of immune function during infection, autoimmunity, or cancer.
2. Immune-mediated induction or inhibition of hypersensitivity in chronic pain or chronic itch.
3. Pathogen-mediated effects on sensory neuron function and the impact on subsequent immune responses to the pathogen.
There are numerous levels of overlap between the nervous and immune systems. This includes shared production of effector molecules and shared expression of receptors, allowing nerve cells to respond to cytokines produced by immune cells, and allowing immune cells to directly sense and respond to neurotransmitters. Both of these systems facilitate the protection of the organism, the nervous system by removal and avoidance of noxious triggers, and the immune system through the targeting and elimination of invading pathogens. Despite the high degree of interaction between these two systems, the investigation of how these disseminated organs interact and influence one another is only beginning to be explored.
Recent discoveries have highlighted this interaction in numerous organ systems, including the skin, mucosal barrier tissues, and secondary lymphoid organs. In the skin, researchers have found substance P and calcitonin gene-related peptide (CGRP) released from sensory neurons influences the type of immune response induced locally and can improve immune resistance by activating innate-like cell types such as gd T cells and Langerhans cells. In some cases, pathogens have hijacked the sensory nervous system in order to evade immune responses and facilitate their persistence in their host. For example, streptococcus pyogenes activates sensory neurons to induce the release of CGRP, which inhibits the recruitment of neutrophils and promotes the survival of the bacteria.
Communication between immune cells and the nervous system is bidirectional; sensory nerves express receptors for inflammatory cytokines, including IL-1b and TNFa, released from the immune system, allowing the nervous system to survey and monitor ongoing immune responses. Signaling by these proinflammatory cytokines sensitizes these sensory nerve fibers and can lead to chronic pain, Furthermore, there is increasing evidence that T cells participate in sensory nerve activation and function. In rodent models of chronic pain after nerve injury, loss of T cells reduced hypersensitivity after nerve injury.
In addition to receptors for substance P and CGRP, both adaptive and innate immune cells also express receptors for catecholamines and acetylcholine released from the sympathetic and parasympathetic arms of the nervous system, respectively. The actions of these neurotransmitters on immune function are complex and often contradictory, likely due to the wide diversity of receptors expressed by immune cells. In addition to neuronally-derived catecholamines and acetylcholine, immune cells are also capable of producing these neurotransmitters during the course of an immune response. In preclinical models of autoimmune arthritis, catecholamine signaling potentiates disease development early in the response and ameliorates disease symptoms later, highlighting the complexity of understanding how the immune system integrates with the sympathetic nervous system. Likewise, signaling by acetylcholine through the a7 nicotinic acetylcholine receptor inhibits macrophage activation and is protective from lethal inflammation associated with sepsis. However, during disseminated viral infection, acetylcholine produced by T cells is required for efficient migration of these cells into infected tissues, and the elimination of the virus.
In this Research Topic, we will explore three broad themes to better understand the intersection of immunity and neuronal signaling. First, how nervous system signaling can activate and inhibit immune function. Second, how immune cells, in turn, influence neuronal activation and signaling, and third, how pathogens manipulate neuronal signaling to evade immune-mediated elimination.
We welcome authors to submit Original Research, Review, Case Report, Clinical Trial, and Methods article types focusing on, but not limited to:
1. Neurotransmitter-mediated activation or inhibition of immune function during infection, autoimmunity, or cancer.
2. Immune-mediated induction or inhibition of hypersensitivity in chronic pain or chronic itch.
3. Pathogen-mediated effects on sensory neuron function and the impact on subsequent immune responses to the pathogen.
