Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model.
Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model.
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DOI：
10.1371/journal.pone.0093549
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lacroix C
中科院分区：
文献类型：
--
作者：
Dostal A;Gagnon M;Chassard C;Zimmermann MB;O'Mahony L;Lacroix C
在传染病负担高的地区，人们对补铁的安全性提出了担忧，因为肠道内较高的铁浓度可能增加肠病原体感染的风险。本研究的目的是研究肠道病原菌肠沙门氏菌的相互作用。采用固定化儿童肠道菌群与Caco-2/HT29-MTX共培养单层接种的体外结肠发酵系统，研究了不同铁浓度下的鼠伤寒杆菌和肠细胞在缺铁和补铁期间在肠腔中遇到的情况。在含有沙门氏菌的正常、低（2,2'-二吡啶螯合）和高铁（26.5 mg铁/L）发酵条件下获得的结肠发酵废液或具有类似铁条件的纯沙门氏菌培养物应用于细胞单层。评估沙门氏菌的粘附和侵袭能力、细胞完整性和免疫反应。在纯培养的高铁条件下，沙门氏菌的粘附力比正常铁条件下增加了8倍，但不影响入侵，导致入侵效率下降（- 86%）。此外，高铁条件下THP-1细胞的细胞因子IL-1β、IL-6、IL-8和TNF-α的分泌以及NF-κB的活化均减弱。纯培养低铁条件下沙门氏菌入侵增加与IL-8释放增加相关。在发酵出水中，沙门氏菌的黏附率比纯培养降低了12倍，侵染率降低了428倍。高铁发酵废液中沙门氏菌的入侵效率（- 77.1%）和细胞TNF-α释放量均低于正常铁废液。与纯培养物相比，发酵流出物中共生微生物群和细菌代谢物的存在减少了沙门氏菌的粘附和入侵，这突出了肠道微生物群在病原体入侵过程中作为屏障的重要性。在补铁过程中，肠道内的高铁浓度降低了沙门氏菌的入侵效率和细胞免疫反应，这表明仅高铁浓度可能不会导致沙门氏菌入侵增加。
In regions with a high infectious disease burden, concerns have been raised about the safety of iron supplementation because higher iron concentrations in the gut lumen may increase risk of enteropathogen infection. The aim of this study was to investigate interactions of the enteropathogen Salmonella enterica ssp. enterica Typhimurium with intestinal cells under different iron concentrations encountered in the gut lumen during iron deficiency and supplementation using an in vitro colonic fermentation system inoculated with immobilized child gut microbiota combined with Caco-2/HT29-MTX co-culture monolayers. Colonic fermentation effluents obtained during normal, low (chelation by 2,2'-dipyridyl) and high iron (26.5 mg iron/L) fermentation conditions containing Salmonella or pure Salmonella cultures with similar iron conditions were applied to cellular monolayers. Salmonella adhesion and invasion capacity, cellular integrity and immune response were assessed. Under high iron conditions in pure culture, Salmonella adhesion was 8-fold increased compared to normal iron conditions while invasion was not affected leading to decreased invasion efficiency (−86%). Moreover, cellular cytokines IL-1β, IL-6, IL-8 and TNF-α secretion as well as NF-κB activation in THP-1 cells were attenuated under high iron conditions. Low iron conditions in pure culture increased Salmonella invasion correlating with an increase in IL-8 release. In fermentation effluents, Salmonella adhesion was 12-fold and invasion was 428-fold reduced compared to pure culture. Salmonella in high iron fermentation effluents had decreased invasion efficiency (−77.1%) and cellular TNF-α release compared to normal iron effluent. The presence of commensal microbiota and bacterial metabolites in fermentation effluents reduced adhesion and invasion of Salmonella compared to pure culture highlighting the importance of the gut microbiota as a barrier during pathogen invasion. High iron concentrations as encountered in the gut lumen during iron supplementation attenuated Salmonella invasion efficiency and cellular immune response suggesting that high iron concentrations alone may not lead to an increased Salmonella invasion.
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影响因子：
4.2
作者：
Burkholder KM;Bhunia AK
通讯作者：
Bhunia AK
影响因子：
3.7
作者：
Kortman GA;Boleij A;Swinkels DW;Tjalsma H
通讯作者：
Tjalsma H
影响因子：
64.8
作者：
Fukuda, Shinji;Toh, Hidehiro;Ohno, Hiroshi
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Ohno, Hiroshi
影响因子：
24.5
作者：
Haller, D;Bode, C;Blum, S
通讯作者：
Blum, S
影响因子：
4.2
作者：
Foster, SL;Richardson, SH;Failla, ML
通讯作者：
Failla, ML