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. Author manuscript; available in PMC: 2015 Aug 13.
Published in final edited form as: Nat Rev Immunol. 2009 Jun;9(6):418–428. doi: 10.1038/nri2566

Figure 1. Neural circuitry of the inflammatory reflex.

Figure 1

The inflammatory reflex controls innate immune responses by a mechanism that targets the regulatory transcription factor nuclear factor-κB (NF-κB). Exogenous and endogenous molecular products of infection and injury interact with receptors that are expressed by cells of the innate immune system, including Toll-like receptors (TLRs) and NLRs (nucleotide-binding domain, leucine-rich-repeat-containing family, such as NALPs (NACHT-, LRR- and PYD-domain containing proteins) and nucleotide-binding oligomerization domain (NOD)-like receptors). Ligand–receptor interactions activate innate immune responses and induce the secretion of pro-inflammatory cytokines. These molecules also activate afferent sensory neurons, which constitute the sensory arc of the inflammatory reflex. Axons travelling in the vagus nerve relay this information as action potentials to the brain stem. This in turn activates the efferent arc, which is known as the cholinergic anti-inflammatory pathway. This inhibits innate immune responses in the spleen through inhibitory signals that arise in the brain stem, traverse the vagus nerve and signal through nicotinic acetylcholine receptor subunit α7 (α7nAChR), which is expressed by cytokine-producing immune cells. This leads to the suppression of NF-κB activation and the inhibition of innate immune responses. Note that the initiation of the inflammatory reflex by many possible ligands through key receptors is a crucial point of innate immune control. So, information from many stimulating molecules is processed by a smaller number of pattern recognition receptors that transduce signalling information to a small number of transcription factors, including NF-κB, that regulate innate immune responses. Maximal control is thereby derived from a circuit in which the inflammatory reflex targets this restricted point of information processing. dsRNA, double-stranded RNA; HMGB1, high-mobility group box 1 protein; IκB, inhibitor of NF-κB; IL-1α, interleukin 1α.