Silvestre Anne, Plaze Aurélie, Berthon Patricia, Thibeaux Roman, Guillen Nancy, Labruyère Elisabeth
Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, F-75015 Paris, France. ; INSERM U786, F-75015 Paris, France. ; INRA, UMR1282 Infectiologie et Santé Publique, F-37380 Nouzilly, France. ; Université de Tours, UMR1282 Infectiologie et Santé Publique, F-37000 Tours, France.
Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, F-75015 Paris, France. ; INSERM U786, F-75015 Paris, France.
Microb Cell. 2015 Jul 6;2(7):235-246. doi: 10.15698/mic2015.07.214.
cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for , and the parasite may have a TNF receptor at its cell surface.
confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and .
an antibody against human TNF receptor 1 (TNFR1) stained the trophozoite surface and (on immunoblots) binds to a 150-kDa protein. Proteome screening with the TNFR1 sequence revealed a BspA family protein in that carries a TNFR signature domain and six leucine-rich repeats (named here as "cell surface protein", CSP, in view of its cellular location). Cell surface protein shares structural homologies with Toll-Like receptors, colocalizes with TNF and is internalized in TNF-containing vesicles. Reduction of cellular CSP levels abolished chemotaxis toward TNF and blocked parasite invasion of human colon.
there is a clear link between TNF chemotaxis, CSP and pathogenesis.
细胞迁移对于人类阿米巴病(一种以组织侵袭和破坏为特征的传染病)的发展至关重要。宿主细胞分泌肿瘤坏死因子(TNF)所引发的组织炎症是阿米巴病的一个有充分记录的特征。肿瘤坏死因子是一种趋化因子,并且该寄生虫在其细胞表面可能有一个TNF受体。
使用共聚焦显微镜、RNA测序、生物信息学、RNA反义技术以及对人结肠外植体的组织学分析来表征TNF与该寄生虫之间的相互作用。
一种针对人类TNF受体1(TNFR1)的抗体对滋养体表面进行了染色,并且(在免疫印迹上)与一种150 kDa的蛋白质结合。用TNFR1序列进行的蛋白质组筛选在该寄生虫中发现了一种BspA家族蛋白,其带有一个TNFR特征结构域和六个富含亮氨酸的重复序列(鉴于其细胞定位,在此命名为“细胞表面蛋白”,CSP)。细胞表面蛋白与Toll样受体具有结构同源性,与TNF共定位,并被内化到含有TNF的囊泡中。细胞CSP水平的降低消除了对TNF的趋化作用,并阻断了该寄生虫对人结肠的侵袭。
TNF趋化作用、CSP与发病机制之间存在明确的联系。