Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology

Although the nervous and immune systems have been classically considered to modulate physiologically distinct functions, recent evidence points to coordinated activities during neurogenic inflammation. In this perspective, the authors examine the interactions between the peripheral nervous system and the immune response during health and disease. The peripheral nervous and immune systems are traditionally thought of as serving separate functions. The line between them is, however, becoming increasingly blurred by new insights into neurogenic inflammation. Nociceptor neurons possess many of the same molecular recognition pathways for danger as immune cells, and, in response to danger, the peripheral nervous system directly communicates with the immune system, forming an integrated protective mechanism. The dense innervation network of sensory and autonomic fibers in peripheral tissues and high speed of neural transduction allows rapid local and systemic neurogenic modulation of immunity. Peripheral neurons also seem to contribute to immune dysfunction in autoimmune and allergic diseases. Therefore, understanding the coordinated interaction of peripheral neurons with immune cells may advance therapeutic approaches to increase host defense and suppress immunopathology.