Early weaning stress in pigs impairs innate mucosal immune responses to enterotoxigenic E. coli challenge and exacerbates intestinal injury and clinical disease.
Early weaning stress in pigs impairs innate mucosal immune responses to enterotoxigenic E. coli challenge and exacerbates intestinal injury and clinical disease.
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DOI：
10.1371/journal.pone.0059838
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moeser AJ
中科院分区：
文献类型：
--
作者：
McLamb BL;Gibson AJ;Overman EL;Stahl C;Moeser AJ
早期生活压力会对人类和动物的肠道疾病的临床发病和严重程度产生深远的影响。在这里，我们研究了猪早期断奶应激对肠道生理、临床疾病和随后用肠毒素F18大肠杆菌(ETEC)攻击的免疫反应的影响。16日龄、18日龄和20日龄断奶的仔猪在26日龄时直接口服F18ETEC。从感染后0-4天监测猪的临床疾病体征。在ETEC攻击后第4天，对回肠黏膜进行回肠屏障功能、组织病理学和炎性细胞因子分析。与早期断奶仔猪(20日龄)相比，早期断奶仔猪(16d和18d断奶)表现出更快的腹泻发病和严重程度，以及对ETEC攻击的反应体重增加减少。ETEC攻击导致早期断奶仔猪的肠屏障损伤，表现为早期断奶仔猪回肠跨上皮电阻值(TER)的降低和FD4流量的增加，但在晚期断奶仔猪中没有。ETEC诱导晚期断奶仔猪IL-6和IL-8显著升高，中性粒细胞募集和肥大细胞激活；这些反应在早期断奶仔猪中减弱。ETEC攻击早期断奶仔猪回肠黏膜中的肿瘤坏死因子水平升高，但在其他断奶日龄组中不升高。这些数据表明，早期断奶应激可以深刻地改变随后的免疫和生理反应以及对后续感染病原体挑战的临床结果。鉴于早期生活应激与动物和人类胃肠道疾病之间的联系，对早期生活应激影响随后的病理生理肠道反应的机制有更基本的了解，这对于预防和处理人类和动物的重要胃肠道疾病具有重要意义。
The clinical onset and severity of intestinal disorders in humans and animals can be profoundly impacted by early life stress. Here we investigated the impact of early weaning stress in pigs on intestinal physiology, clinical disease, and immune response to subsequent challenge with enterotoxigenic F18 E. coli (ETEC). Pigs weaned from their dam at 16 d, 18 d, and 20 d of age were given a direct oral challenge of F18 ETEC at 26 d of age. Pigs were monitored from days 0 to 4 post-infection for clinical signs of disease. On Day 4 post-ETEC challenge, ileal barrier function, histopathologic and inflammatory cytokine analysis were performed on ileal mucosa. Early weaned pigs (16 d and 18 d weaning age) exhibited a more rapid onset and severity of diarrhea and reductions in weight gain in response to ETEC challenge compared with late weaned pigs (20 d weaning age). ETEC challenge induced intestinal barrier injury in early weaned pigs, indicated by reductions in ileal transepithelial electrical resistance (TER) and elevated FD4 flux rates, in early weaned pig ileum but not in late weaned pigs. ETEC-induced marked elevations in IL-6 and IL-8, neutrophil recruitment, and mast cell activation in late-weaned pigs; these responses were attenuated in early weaned pigs. TNF levels elevated in ETEC challenged ileal mucosa from early weaned pigs but not in other weaning age groups. These data demonstrate the early weaning stress can profoundly alter subsequent immune and physiology responses and clinical outcomes to subsequent infectious pathogen challenge. Given the link between early life stress and gastrointestinal diseases of animals and humans, a more fundamental understanding of the mechanisms by which early life stress impacts subsequent pathophysiologic intestinal responses has implications for the prevention and management of important GI disorders in humans and animals.
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影响因子：
3.7
作者：
Loos M;Geens M;Schauvliege S;Gasthuys F;van der Meulen J;Dubreuil JD;Goddeeris BM;Niewold T;Cox E
通讯作者：
Cox E
影响因子：
64.8
作者：
Malaviya, R;Ikeda, T;Abraham, SN
通讯作者：
Abraham, SN
DOI：
10.1152/ajpgi.00304.2006
发表时间：
2007-08-01
影响因子：
4.5
作者：
Moeser, Adam J.;Ryan, Kathleen A.;Blikslager, Anthony T.
通讯作者：
Blikslager, Anthony T.
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Dapoigny, M.
通讯作者：
Dapoigny, M.