Neuroimmune Communication in Health and Disease

Abstract

The immune and nervous systems are tightly integrated, with each system capable of influencing the other to respond to infectious or inflammatory perturbations of homeostasis. Recent studies demonstrating the ability of neural stimulation to significantly reduce the severity of immunopathology and consequently reduce mortality have led to a resurgence in the field of neuroimmunology. Highlighting the tight integration of the nervous and immune systems, afferent neurons can be activated by a diverse range of substances from bacterial-derived products to cytokines released by host cells. While activation of vagal afferents by these substances dominates the literature, additional sensory neurons are responsive as well. It is becoming increasingly clear that although the cholinergic anti-inflammatory pathway has become the predominant model, a multitude of functional circuits exist through which neuronal messengers can influence immunological outcomes. These include pathways whereby efferent signaling occurs independent of the vagus nerve through sympathetic neurons. To receive input from the nervous system, immune cells including B and T cells, macrophages, and professional antigen presenting cells express specific neurotransmitter receptors that affect immune cell function. Specialized immune cell populations not only express neurotransmitter receptors, but express the enzymatic machinery required to produce neurotransmitters, such as acetylcholine, allowing them to act as signaling intermediaries. Although elegant experiments have begun to decipher some of these interactions, integration of these molecules, cells, and anatomy into defined neuroimmune circuits in health and disease is in its infancy. This review describes these circuits and highlights continued challenges and opportunities for the field.

The sympathetic nervous system in acute kidney injury

“…10 During acute renal ischaemia, the activity of renal sensory nerves was found to be elevated. 25,26,36 Visceral spinal afferent neurons including nociceptors can be activated by substances released from damaged tissues (so called damage or danger-associated molecular patterns, DAMPs); 8 Unilateral after UNX 1 44 Unilateral without UNX 1 31 Rat Bilateral 2 45,54 Unilateral after UNX 13 20,[23][24][25]27,28,[33][34][35]46,50,69,73 Unilateral without UNX 3 26,39,52 Rabbit Unilateral after UNX 2 42,43 Dog Unilateral after UNX 1 49 Abbreviation: UNX, uninephrectomy.…”

“…1,5 Pathologic states that lead to AKI are frequently associated with acute activation of the sympathetic nervous system (SNS) and the development of AKI in turn may cause sympathetic activation. [7][8][9] The present article reviews the current state on the role of SNS overactivity in AKI focusing on renal ischaemia reperfusion (IR). 6 Evidence is accumulating that interactions between the autonomic nervous system and the immune system are involved in the pathogenesis of multiple forms of organ damage.…”

“…6 Evidence is accumulating that interactions between the autonomic nervous system and the immune system are involved in the pathogenesis of multiple forms of organ damage. [7][8][9] The present article reviews the current state on the role of SNS overactivity in AKI focusing on renal ischaemia reperfusion (IR). Causes of sympathetic activation in response to IR will be identified.…”

DJ-1 (Park7) affects the gut microbiome, metabolites and development of Innate Lymphoid cells (ILCs)

“…Recent studies in PD patients have described the potential link with gut microbial abundance and Parkinson's pathogenesis (28,29,31). Further findings suggested that the brain-gut axis interactions are controlled by the gut microbiome through immunological, neuroendocrine and direct neural mechanisms, respectively (19,39). Therefore, a clear understanding of the microbiota-gut-brain axis interaction could bring a new insights in the pathophysiology of PD and allow an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system (41).…”

“…Immune cells are capable of engaging in direct communication with enteric neurons (18,20). The extent of the functional impact of neuro-immune synapses is not clear yet however published studies advocated that activated immune cells can temper neuronal activity via the release of neurotransmitters, metabolites and cytokines (19,39,40). Based on the common occurrence of GIT symptoms in PD, dysbiosis among PD patients, and evidence that the microbiota impacts CNS function, we hypothesized that DJ-1 protein could also be involved in the regulation of the gut microbiome and inflammation.…”