John Daniel A, Williams Lisa K, Kanamarlapudi Venkateswarlu, Humphrey Thomas J, Wilkinson Thomas S
Microbiology and Infectious Disease, Swansea University Medical School, Institute of Life Science, Swansea University, Swansea, United Kingdom.
Cellular Biology, Swansea University Medical School, Institute of Life Science, Swansea University, Swansea, United Kingdom.
Front Microbiol. 2017 Sep 29;8:1840. doi: 10.3389/fmicb.2017.01840. eCollection 2017.
remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took isolates ( = 100) from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. induced diverse cytotoxic responses in both cell lines with -positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the species.
在发达国家,仍是人类肠胃炎的主要病因,给卫生服务带来了沉重负担。是人类和鸡的病原体,尽管对其作用机制的理解差异尚不完全清楚,部分原因是表型菌株多样性导致研究结果不一致。在这里,我们从多位点序列分型的集合中选取了100株分离株,通过在使用禽类和人类肠道上皮细胞的高通量模型中观察它们的炎症、细胞毒性、黏附、侵袭和信号反应,来评估它们的致病多样性。分别以丝裂原活化蛋白激酶依赖的方式在人类和禽类上皮细胞中诱导白细胞介素-8(IL-8)和CXCLi1/2。相比之下,两种细胞类型中的白细胞介素-10反应是磷脂酰肌醇3-激酶/蛋白激酶B(PI 3-激酶/Akt)依赖的。菌株在两种细胞系中显示出不同程度的侵袭,高侵袭依赖于丝裂原活化蛋白激酶信号传导。在两种细胞系中诱导了不同的细胞毒性反应,携带特定基因的阳性分离株显示出明显更高的毒性。对胞吞途径的阻断表明,在两种细胞中,的侵袭依赖于网格蛋白和发动蛋白,但不依赖于小窝蛋白。相比之下,IL-8(和CXCLi1/2)的产生依赖于网格蛋白、发动蛋白和小窝蛋白。这项研究因其规模和所产生的数据而具有重要意义,表明禽类和人类上皮细胞使用相似的固有免疫途径,其中反应的强度由该物种的表型多样性决定。