Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Apartado Postal 14-740, México, DF 07360, Mexico.
Int J Parasitol. 2011 Aug 15;41(10):1101-12. doi: 10.1016/j.ijpara.2011.06.003. Epub 2011 Jul 13.
In mixed intestinal infections with Entamoeba histolytica trophozoites and enteropathogenic bacteria, which are wide-spread in areas of endemic amoebiasis, interaction between the pathogens could be an important factor in the occurrence of invasive disease. It has been reported that exposure of human colonic cells to enteropathogenic bacteria increased trophozoite adherence to the cells and their subsequent damage. We report here that the Carbohydrate Recognition Domain (CRD) of the amoebic Gal/GalNAc lectin binds to Toll-like receptors TLR-2 and TLR-4 in human colonic cells, activating the "classic" signalling pathway of these receptors. Activation induced expression of TLR-2 and TLR-4 mRNAs and the mRNAs of pro-inflammatory cytokines, as well as an increase in the corresponding proteins. Direct correlation was observed between the increased expression of TLRs and pro-inflammatory cytokines, the enhanced adhesion of trophozoites to the cells and the inflicted cell damage. When cells were exposed to pathogenic bacteria Staphylococcus aureus (Gram⁺) or Shigella dysenteriae (Gram⁻), elements of an innate immune response were induced. CRD by itself elicited a similar cell response, while exposure to a commensal Escherichia coli had a null effect. Pre-exposure of the cells to pathogenic bacteria and then to CRD rendered an inflammatory-like microenvironment that after addition of trophozoites facilitated greater cell destruction. Our results suggest that CRD is recognised by human colonic cells as a pathogen-associated-molecular-pattern-like molecule and as such can induce the expression of elements of an innate immune response. In the human host, an exacerbated inflammatory environment, derived from pathogen interplay, may be an important factor for development of invasive disease.
在伴有溶组织内阿米巴滋养体和肠道致病菌的混合性肠道感染中，这些病原体在地区性阿米巴病流行地区广泛存在，病原体之间的相互作用可能是侵袭性疾病发生的一个重要因素。据报道，暴露于肠道致病菌的人结肠细胞会增加滋养体对细胞的黏附和随后的损伤。我们在此报告，原虫的半乳糖/ N-乙酰半乳糖凝集素的碳水化合物识别结构域（CRD）与人结肠细胞中的 Toll 样受体 TLR-2 和 TLR-4 结合，激活这些受体的“经典”信号通路。激活诱导 TLR-2 和 TLR-4 的 mRNA 和促炎细胞因子的 mRNA 的表达，以及相应蛋白的增加。观察到 TLR 和促炎细胞因子的表达增加、滋养体与细胞的黏附增强和细胞损伤之间存在直接相关性。当细胞暴露于致病性细菌金黄色葡萄球菌（革兰氏阳性菌）或痢疾志贺菌（革兰氏阴性菌）时，诱导了先天免疫反应的元素。CRD 本身会引起类似的细胞反应，而暴露于共生的大肠杆菌则没有这种作用。细胞预先暴露于致病性细菌，然后再暴露于 CRD，会产生类似炎症的微环境，然后添加滋养体后会更容易导致细胞破坏。我们的结果表明，CRD 被人结肠细胞识别为一种病原体相关分子模式样分子，因此可以诱导先天免疫反应元素的表达。在人类宿主中，源自病原体相互作用的加剧炎症环境可能是侵袭性疾病发展的一个重要因素。
