Acetylcholine Regulates Inflammation and Tissue Repair during Respiratory Viral Infection

Acetylcholine acts as a powerful anti-inflammatory agent in the brain/immune circuit known as the cholinergic anti-inflammatory pathway. Acetylcholine binding to a7 nicotinic acetylcholine receptors on tissue macrophages decrease nuclear translocation of the critical transcription factor Nf-kB. This decreases ongoing production of inflammatory cytokines such as TNF, IL1b, and IL6. In the spleen, acetylcholine production by CD4T cells is a critical protective factor in preventing lethal sepsis. We explored the role of acetylcholine and cholinergic lymphocytes in the lungs during influenza, expecting that acetylcholine would be produced in response to the innate immune inflammatory burst. Instead, we found that airway acetylcholine concentration increased between days 8-11 post-infection. This coincided with the appearance of cholinergic CD4 T cells and conventional B cells. When acetylcholine production was inhibited, pulmonary inflammation was increased, and recovery was delayed. Furthermore, the lungs showed evidence of aberrant tissue repair. Conversely, increasing acetylcholine blocks influenza-associated morbidity. These results indicate the unsuspected role of acetylcholine and cholinergic lymphocytes in regulating macrophage-mediated inflammation and pulmonary repair during recovery from respiratory viral infection. Moderator: James A. Glazier, PhD, Indiana University, Bloomington To learn more see: Horkowitz, Alexander P., Ashley V. Schwartz, Carlos A. Alvarez, Edgar B. Herrera, Marilyn L. Thoman, Dale A. Chatfield, Kent G. Osborn, Ralph Feuer, Uduak Z. George, and Joy A. Phillips. "Acetylcholine regulates pulmonary pathology during viral infection and recovery." ImmunoTargets and therapy (2020): 333-350. https://www-tandfonline-com.proxyiub.uits.iu.edu/doi/full/10.2147/ITT.S279228 *Contents* 00:00 - Introduction 07:06 - Joy Phillips: Acetylcholine Regulates Inflammation and Tissue Repair during Respiratory Viral Infection 39:26 - Discussion To view the slides in this video, visit: https://drive.google.com/file/d/10KqwfcO-6oeigUVIXb2BhXGlyjIr4mLy/ If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://tinyurl.com/GLIMPRINTVideos Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings Please also consider joining the Global Alliance for Immune Prediction and Intervention: http://glimprint.org/