Cholinergic Activation Enhances Resistance to Oral Salmonella Infection by Modulating Innate Immune Defense Mechanisms at the Intestinal Barrier

Frontiers in Immunology

Saeed Tariq¹  Ray M. Al-Barazie²  Mohammed M. Qureshi²  Maria J. Fernandez-Cabezudo²  Basel K. al-Ramadi³  Yassir A. Mohamed³  Ghada Hassan Bashir³  Ashraf Al-Sbiei³  Wim J. Lammers⁴ 

[1] Department of Anatomy, College of Medicine and Health Sciences, United Arab University, Al-Ain, United Arab Emirates;Department of Biochemistry, College of Medicine and Health Sciences, United Arab University, Al-Ain, United Arab Emirates;Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab University, Al-Ain, United Arab Emirates;Department of Physiology, College of Medicine and Health Sciences, United Arab University, Al-Ain, United Arab Emirates;

关键词: acetylcholine;    cholinergic pathway;    Salmonella infection;    mucosal innate immunity;    antimicrobial peptides;    Paneth cells;   

DOI  :  10.3389/fimmu.2018.00551

来源: DOAJ

【 摘 要 】

Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated through immunological and neural pathways. Previously, we demonstrated that cholinergic stimulation confers enhanced protection in experimental animals orally infected with virulent Salmonella enterica serovar Typhimurium. In this study, we investigated the mechanism by which this enhanced protection takes place. Cholinergic stimulation was induced by a 3-week pretreatment with paraoxon, a highly specific acetylcholinesterase (AChE) inhibitor. This treatment enhanced host survival following oral-route infection and this correlated with significantly reduced bacterial load in systemic target organs. Enhanced protection was not due to increased gut motility or rapid bacterial clearance from the gastrointestinal tract. Moreover, protection against bacterial infection was not evident when the animals were infected systemically, suggesting that acetylcholine-mediated protective effect was mostly confined to the gut mucosal tissue. In vivo imaging demonstrated a more localized infection and delay in bacterial dissemination into systemic organs in mice pretreated with paraoxon. Morphological analysis of the small intestine (ileum) showed that AChE inhibition induced the degranulation of goblet cells and Paneth cells, two specialized secretory cells involved in innate immunity. Our findings demonstrate a crucial pathway between neural and immune systems that acts at the mucosal interface to protect the host against oral pathogens.

【 授权许可】

Unknown