Sensory neurons: An integrated component of innate immunity

Deng, Liwen; Gillis, Jacob E.; Chiu, Isaac M.; Kaplan, Daniel H.

doi:10.1016/j.immuni.2024.03.008

Cited by 4 publications

(2 citation statements)

References 127 publications

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“…These results suggest that SP receptor signaling enhances colonic T-cell recruitment by increasing MAdCAM-1 on the surface of endothelial cells. Although SP has been reported to increase adhesion molecule expression such as ICAM-1 and VCAM-1 28,36,38 , SP receptor antagonism did not reduce these cellular adhesion molecules induced by C. rodentium infection. It is critical to note that the SP-induced ICAM-1 and VCAM-1 expression were conducted on human dermal microvascular endothelial cells, or endothelial cell lines in vitro 36,37 .…”

Section: Discussionmentioning

confidence: 73%

“…Host-protective responses elicited by pathogens in the intestinal tract are tightly controlled and require a diverse array of cell types. Coordination of these responses can occur through many cell-intrinsic and cell-cell communication networks 28 . Neurotransmitters released by the neurons within the intestinal tract have become increasingly recognized to exert not only control over intestinal physiology but also immune function.…”

Section: Discussionmentioning

confidence: 99%

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Substance P receptor signaling contributes to host maladaptive responses during enteric bacterial infection

Cremin,

Ramirez,

Sanchez

et al. 2024

Preprint

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Immune responses in the intestine are intricately balanced to prevent pathogen entry without inducing immunopathology. The nervous system is well-established to interface with the immune system to fine-tune immunity in various organ systems including the gastrointestinal tract. Specialized sensory neurons can detect bacteria, bacterial products, and the resulting inflammation, to coordinate the immune response in the gastrointestinal tract. These sensory neurons release peptide neurotransmitters such as Substance P (SP), to induce both neuronal signaling and localized responses in non-neuronal cells. With this in mind, we assessed the immunoregulatory roles of SP receptor signaling during enteric bacterial infection with the non-invasive pathogenCitrobacter rodentium. Pharmacological antagonism of the SP receptor significantly reduced bacterial burden and prevented colonic crypt hyperplasia. Mice with SP receptor signaling blockade had significantly reduced inflammation and recruitment of T-cells in the colon. Reduced colonic T-cell recruitment is due to reduced expression of adhesion molecules on colonic endothelial cells in SP receptor antagonist-treated mice. Using SP receptor T-cell conditional knockout mice, we further confirmed SP receptor signaling enhanced select aspects of T-cell responses. Our data demonstrates that SP receptor signaling can significantly reduce inflammation and prevent host-maladaptive responses without impinging upon host protection.

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