Investigating the role of t cell-derived acetylcholine during influenza a virus infection
Active Project Grant Awarded Last action
- Award ID
- F31AI197827
- Recipient
-
University Of Oklahoma UEI GY8NMUZQXVS7
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $95,828
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 3% complete
- Place of performance
- Oklahoma City, OK 73104, USA
Award details come from USAspending.gov.
Description
- Abstract
- The neurotransmitter acetylcholine regulates a diverse range of physiological functions and IT is known that immune cells can respond to and synthesize acetylcholine in response to viral infections. Within the influenza a virus (IAV) infected lung, t cells are recruited to combat the infection. Upon an IAV infection activated t cells induce the gene choline acetyltransferase (chat) which results in the production of acetylcholine. I have found that aged mice are less likely to survive IAV infection and have fewer chat+ IAV-specific t cells than young mice. However, IT is unclear why this decrease happens in aging mice. Humans over the age of 65 become hyper susceptible to IAV infection, while this is traditionally attributed to the changes in the immune landscape and quiescence of the immune system, little is known if there are other contributing factors. Using a mouse model wherein chat is not expressed in t cells i found that young mice that cannot produce t cell-derived acetylcholine have decreased survival and defective recovery from IAV infection. However, these mice clear IAV normally and have no differences in t cell infiltration into the lungs. Instead, i found that inflammation in the lungs is sustained well after viral clearance when t cells cannot produce acetylcholine. While this inflammation could be driven by many immune cell types, the only significantly elevated immune cell type in the lungs are neutrophils. Neutrophil depletion in vivo in the mice unable to synthesize t cell-derived acetylcholine rescues recovery. Additionally, the in vitro presence of acetylcholine prevents neutrophil migration toward a chemoattractant. This observation indicates a direct effect of t cell-derived acetylcholine on neutrophils. Taken together, these results suggest that acetylcholine-producing t cells are a critical source of acetylcholine in the lung during recovery from influenza infection. This proposal seeks to understand if (1) epigenetic changes are responsible for the decrease in chat expression in aged mice, (2) inhibiting the breakdown of acetylcholine can rescue weight recovery, and (3) how neutrophils are being directly impacted by t cell-derived acetylcholine. Based on my preliminary studies i hypothesize that acetylcholine plays a central role in recovery from viral infection. This hypothesis will be tested in the following aims.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $47,914 | |
| Amendment | $47,914 | |
| Original award | $0 |
Quick answers
Who received award F31AI197827?
F31AI197827 was awarded to University Of Oklahoma by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on October 21, 2026.
How much is award F31AI197827 worth?
$95,828 has been obligated on F31AI197827.
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