Sensory neurons: An integrated component of innate immunity

Abstract

The sensory nervous system possesses the ability to integrate exogenous threats and endogenous signals to mediate downstream effector functions. Sensory neurons have been shown to activate or suppress host defense and immunity against pathogens, depending on the tissue and disease state. Through this lens, pro- and anti-inflammatory neuroimmune effector functions can be interpreted as evolutionary adaptations by host or pathogen. Here, we discuss recent and impactful examples of neuroimmune circuitry that regulate tissue homeostasis, autoinflammation, and host defense. Apparently paradoxical or conflicting reports in the literature also highlight the complexity of neuroimmune interactions that may depend on tissue- and microbe-specific cues. These findings expand our understanding of the nuanced mechanisms and the greater context of sensory neurons in innate immunity.

Keywords: barrier immunity; host defense; innate immunity; neuroimmune; neurons; sensory.

Figure 1.. Sensory neurons participate in innate immunity.

(A) Neurons can detect endogenous and exogenous signals of infections, inflammation, and tissue damage and release neuropeptides and neurotransmitters to regulate immune responses. (B) Sensory neuron cell bodies reside in ganglia and their peripheral nerve terminals innervate barrier tissues.

Figure 2.. Neuroimmune signaling in tissue homeostasis.

(A) Sensory neurons drive homeostasis in the gut. (B) Immune cells crosstalk with microbes promotes sensory neuron growth during wound healing.

Figure 3.. Neuroimmune communication regulate autoinflammation and allergy.

(A) SP⁺ peptidergic neurons and Glutamate⁺ non-peptidergic neurons antagonistically regulate mast cell reactivity in the skin. Independent of mast cells, SP also drives dendritic cells to promote a Th2 response at the dLN. (B) Sensory neurons regulate lung inflammation through the neuropeptides VIP and CGRPβ. (C) Neuropeptide NMU promotes a Type-2 innate immune response in the lung and gut by activating ILC2s that are constrained by neuronally derived and autocrine CGRP. (D) Feeding promotes the release of VIP from enteric neurons. VIP acts on IL-22⁺ ILCs and regulates the balance between nutrient uptake and barrier defense

Figure 4.. Neurons crosstalk with microbes and immune cells in host defense against.

(A) Sensory neurons are directly activated by bacterial toxins and drive behavioral reflexes. (B) Bacteria can hijack neuro-immune signaling to induce pain and limit inflammation. (C) TRPV1⁺ neurons enhance cutaneous immune responses to pathogens and promote anticipatory immunity in adjacent skin regions.

Figure 5.. Neuronal control of immunity is evolutionarily conserved.

(A) Sensory neurons promote defense against pathogens in C. elegans. (B) Neurons regulate tissue repair in the D. melanogaster gut.