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Horkowitz AP, Schwartz AV, Alvarez CA, et al. Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery. Immunotargets Ther. 2020;9:333-350doi: 10.2147/ITT.S279228.
Horkowitz, A. P., Schwartz, A. V., Alvarez, C. A., Herrera, E. B., Thoman, M. L., Chatfield, D. A., Osborn, K. G., Feuer, R., George, U. Z., & Phillips, J. A. (2020). Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery. ImmunoTargets and therapy, 9333-350. https://doi.org/10.2147/ITT.S279228
Horkowitz, Alexander P, et al. "Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery." ImmunoTargets and therapy vol. 9 (2020): 333-350. doi: https://doi.org/10.2147/ITT.S279228
Horkowitz AP, Schwartz AV, Alvarez CA, Herrera EB, Thoman ML, Chatfield DA, Osborn KG, Feuer R, George UZ, Phillips JA. Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery. Immunotargets Ther. 2020 Dec 17;9:333-350. doi: 10.2147/ITT.S279228. eCollection 2020. PMID: 33365281; PMCID: PMC7751717.
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Immunotargets Ther. 2020 Dec 17;9:333-350. doi: 10.2147/ITT.S279228. eCollection 2020.

Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery.

ImmunoTargets and therapy

Alexander P Horkowitz, Ashley V Schwartz, Carlos A Alvarez, Edgar B Herrera, Marilyn L Thoman, Dale A Chatfield, Kent G Osborn, Ralph Feuer, Uduak Z George, Joy A Phillips

Affiliations

  1. Donald P. Shiley Biosciences Center, San Diego State University, San Diego, California, USA.
  2. Department of Biology, San Diego State University, San Diego, California, USA.
  3. Department of Mathematics and Statistics, San Diego State University, San Diego, California, USA.
  4. Department of Chemistry, San Diego State University, San Diego, California, USA.
  5. Office of Animal Research, University of California San Diego, San Diego, California, USA.

PMID: 33365281 PMCID: PMC7751717 DOI: 10.2147/ITT.S279228

Abstract

INTRODUCTION: This study was designed to explore the role of acetylcholine (ACh) in pulmonary viral infection and recovery. Inflammatory control is critical to recovery from respiratory viral infection. ACh secreted from non-neuronal sources, including lymphocytes, plays an important, albeit underappreciated, role in regulating immune-mediated inflammation.

METHODS: ACh and lymphocyte cholinergic status in the lungs were measured over the course of influenza infection and recovery. The role of ACh was examined by inhibiting ACh synthesis in vivo. Pulmonary inflammation was monitored by Iba1 immunofluorescence, using a novel automated algorithm. Tissue repair was monitored histologically.

RESULTS: Pulmonary ACh remained constant through the early stage of infection and increased during the peak of the acquired immune response. As the concentration of ACh increased, cholinergic lymphocytes appeared in the BAL and lungs. Cholinergic capacity was found primarily in CD4 T cells, but also in B cells and CD8 T cells. The cholinergic CD4

CONCLUSION: These findings point to a previously unrecognized role for ACh in the transition from active immunity to recovery and pulmonary repair following respiratory viral infection.

© 2020 Horkowitz et al.

Keywords: Aif-1; CD4 resident memory; ChAT; Iba1; MATLAB; acetylcholine; acetylcholinesterase; automated algorithm; cholinergic anti-inflammatory pathway; cholinergic lymphocytes; inflammaging; inflammation; influenza; pulmonary repair

Conflict of interest statement

This study was supported by NIH AI119929 (JP), San Diego State University Bridge Funding (JP), and San Diego State University Initiative for Maximizing Student Development Award GM058906 (CA). The fun

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