The gut immune system shares many mediators and receptors with the autonomic nervous system. Good examples thereof are the parasympathetic (vagal) and sympathetic neurotransmitters, for which many immune cell types in a gut context express receptors or enzymes required for their synthesis. For some of these the relevance for immune regulation has been recently defined. Earlier and more recent studies in neuroscience and immunology have indicated the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. Sympathetic immune modulation is well described earlier, and in the last decade the parasympathetic vagal nerve has been put forward as an integral part of an immune regulation network via its release of Ach, a system coined “the cholinergic anti-inflammatory reflex.” A prototypical example is the inflammatory reflex, comprised of an afferent arm that senses inflammation and an efferent arm: the cholinergic anti-inflammatory pathway, that inhibits innate immune responses. In this paper, the current understanding of how innate mucosal immunity can be influenced by the neuronal system is summarized, and cell types and receptors involved in this interaction will be highlighted. Focus will be given on the direct neuronal regulatory mechanisms, as well as current advances regarding the role of microbes in modulating communication in the gut-brain axis. 1. Introduction 1.1. Innervation and Immunity in the Gastrointestinal Tract It is increasingly acknowledged that the neuroendocrine and, the sympathetic and parasympathetic arms of the autonomic nervous system and the enteric nervous system are the key pathways through which the gut and the brain communicate. The principle is established that the immune system can no longer be regarded as an autonomous functioning entity but clearly receives regulatory input from neuronal systems. The “cholinergic inflammatory neuronal reflex” is one example of how action potentials originating in neurons influence immunity. The lymphoid organs of the immune system are innervated by cholinergic, catecholaminergic, and peptidergic, and other neurons, and many neurotransmitters and receptors are shared between the immune system and the nervous system, substantiating claims of a strong regulatory component of the nervous system in immune responses. A good example thereof is the discovery of acetylcholine producing memory T-cells in the circulation [1, 2] and spleen [3]. It is likely that such cells can interact with other antigen presenting cells or feed back on nerve terminals in
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