Campos-Rodríguez Rafael, Godínez-Victoria Marycarmen, Reyna-Garfias Humberto, Arciniega-Martínez Ivonne Maciel, Reséndiz-Albor Aldo Arturo, Abarca-Rojano Edgar, Cruz-Hernández Teresita Rocío, Drago-Serrano Maria Elisa
Research and Graduate Studies Section, Superior School of Medicine, National Polytechnic Institute, Plan de San Luis y Díaz Mirón s/n, Col. Santo Tomas, CP 11340, México, D.F., México.
Department of Biological Systems, Autonomous Metropolitan University Xochimilco Campus, Calzada del Hueso No 1100, Col. Villa Quietud, CP 04960, México, D.F., México.
Age (Dordr). 2016 Feb;38(1):13. doi: 10.1007/s11357-016-9876-3. Epub 2016 Jan 21.
Intermittent fasting (IF) reportedly increases resistance and intestinal IgA response to Salmonella typhimurium infection in mature mice. The aim of this study was to explore the effect of aging on the aforementioned improved immune response found with IF. Middle-aged male BALB/c mice were submitted to IF or ad libitum (AL) feeding for 40 weeks and then orally infected with S. typhimurium. Thereafter, infected animals were all fed AL (to maximize their viability) until sacrifice on day 7 or 14 post-infection. We evaluated body weight, bacterial load (in feces, Peyer's patches, spleen and liver), total and specific intestinal IgA, lamina propria IgA+ plasma cells, plasma corticosterone, and messenger RNA (mRNA) expression of α-chain, J-chain, and the polymeric immunoglobulin receptor (pIgR) in liver and intestinal mucosa. In comparison with the infected AL counterpart, the infected IF group (long-term IF followed by post-infection AL feeding) generally had lower intestinal and systemic bacterial loads as well as higher total IgA on both post-infection days. Both infected groups showed no differences in corticosterone levels, body weight, or food and caloric intake. The increase in intestinal IgA was associated with enhanced pIgR mRNA expression in the intestine (day 7) and liver. Thus, to maintain body weight and caloric intake, IF elicited metabolic signals that possibly induced the increased hepatic and intestinal pIgR mRNA expression found. The increase in IgA probably resulted from intestinal IgA transcytosis via pIgR. This IgA response along with phagocyte-induced killing of bacteria in systemic organs (not measured) may explain the resolution of the S. typhimurium infection.
据报道,间歇性禁食(IF)可增强成熟小鼠对鼠伤寒沙门氏菌感染的抵抗力和肠道IgA反应。本研究的目的是探讨衰老对IF所带来的上述免疫反应改善的影响。将中年雄性BALB/c小鼠进行40周的IF或随意进食(AL)喂养,然后口服感染鼠伤寒沙门氏菌。此后,所有感染动物均改为AL喂养(以最大程度提高其存活率),直至在感染后第7天或第14天处死。我们评估了体重、细菌载量(粪便、派尔集合淋巴结、脾脏和肝脏中的)、总肠道IgA和特异性肠道IgA、固有层IgA+浆细胞、血浆皮质酮以及肝脏和肠黏膜中α链、J链和多聚免疫球蛋白受体(pIgR)的信使核糖核酸(mRNA)表达。与感染的AL组相比,感染的IF组(长期IF后改为感染后AL喂养)在感染后的两天内,肠道和全身细菌载量通常较低,总IgA较高。两个感染组在皮质酮水平、体重或食物及热量摄入方面均无差异。肠道IgA的增加与肠道(第7天)和肝脏中pIgR mRNA表达增强有关。因此,为维持体重和热量摄入,IF引发了代谢信号,可能诱导了所观察到的肝脏和肠道pIgR mRNA表达增加。IgA的增加可能是由于肠道IgA通过pIgR进行转胞吞作用。这种IgA反应以及吞噬细胞在全身器官中诱导的细菌杀伤作用(未测量)可能解释了鼠伤寒沙门氏菌感染的消退。