Analysis of cholinergic pathway-induced alterations at the intestinal mucosa and their association with enhanced resistance to lethal bacterial infection

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Abstract The mucosal innate immune system represents the first line of defense against microorganisms invading the intestinal tract. Increasing evidence suggests that mucosal immune defenses are tightly regulated by immunological and neural pathways. We previously demonstrated that activation of the cholinergic pathway through the administration of a highly specific acetylcholinesterase inhibitor (AChEI), paraoxon, confers resistance to an oral infection by virulent S. typhimurium. This protection is mediated by enhanced innate anti-microbial mucosal defenses in the GI tract. In the present study, we investigated the involvement of different immune cell populations in the GI tract in the modulation of AChEI-mediated anti-Salmonella resistance. Morphological evaluation of intestinal tissue from control- or AChEI-treated mice revealed a significant thickening of the mucin layer and increased B and T lymphocytic infiltration into intestinal mucosa in the AChEI group. Multi-color flow cytometric analysis of iliac intraepithelial lymphocytes (IELs) showed that cholinergic stimulation increased the percentage of CD3+CD8+gamma/delta TCR+ cells. No significant alterations were observed in lamina propria cells. Our findings indicate that cholinergic pathway is able to modulate not only mucin-secreting cells but more importantly gamma/delta T cells, the cell population known to be involved in tissue homeostasis and repair as well as surveillance of the epithelial barrier.