In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 170.27-170.27
Abstract:
The vagus nerve plays an important role in maintaining an organism’s immune homeostasis through the inflammatory reflex. Inflammatory molecules including LPS, TNF and IL-1β can mediate electrophysiological changes in vagus nerve signaling. Reasoning that these signals are mediated though specific neuronal fibers that can be identified by molecular markers, we administered endotoxin to mice that received optovin, a molecule that interacts with TRPA1 and is light sensitive. Selective stimulation of vagus nerve TRPA1+ fibers significantly reduce serum TNF levels (sham: 920.9 ± 87.9 pg/ml vs. stimulated: 456.8 ± 69.4 pg/ml). This reduction is ablated by proximal vagotomy, indicating that the signals are afferent in nature. Prior work suggests that the afferent vagus nerve is required for IL-1β induced febrile responses and sickness behavior. Here we administered IL-1β to TRPA1 KO mice and observed that body temperature was maintained as compared to wildtype (peak temperature change; wildtype: −2.35 ± 0.15 °C vs. TRPA1 KO:0.18 ± 0.40 °C). When recording electrical activity from the VN, IL-1β induces a significant increase in VN activity in WT mice. However, no significant increase is observed in TRPA1 KOs. Cecal ligation and puncture in TRPA1 KOs caused significantly higher disease severity scores, percent weight loss, and mortality. These results identify TRPA1 as both a marker for fiber specific inflammatory signaling as well as a necessary component for regulating inflammatory homeostasis.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.170.27
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2018
detail.hit.zdb_id:
1475085-5
