Inhibition of acetylcholinesterase regulates the anti-microbial immune response (P1378)

Abstract

Abstract We have previously demonstrated that inhibition of the enzyme acetylcholinesterase, leads to an enhancement of animal survival following an oral infection with a lethal strain of S. typhimurium, a Gram-negative, facultative, intracellular pathogen. We hypothesized that the resultant increase in acetylcholine levels modulates the macrophage inflammatory response to infection. In this study, we assessed the potential of modulating the host’s immune response following a lethal bacterial infection. BALB/c mice were orally infected with a virulent strain of S. typhimurium, following which they were injected i.p. with the acetylcholinesterase inhibitor paraxon. The start of paraoxon injection varied from 30 minutes to 24 hrs post bacterial infection and repeated daily for 7 consecutive days. In contrast to control group which exhibited 10% survival, animals treated with paraoxon up to 6 hrs post infection showed 50% overall survival. Enhanced survival observed in this group correlated with a more robust inhibition of bacterial proliferation in systemic target organs. Furthermore, preliminary evidence from flowcytometric analysis of mesenteric lymph nodes and spleen cell populations revealed an increase in T lymphocyte ratios as well as upregulation of IFN gamma-regulated activation markers on B and T lymphocytes in the paraoxon-treated group. These findings underscore the importance of the neural-immune axis in regulating immunity to bacterial infection.