Pagliuca Chiara, Cicatiello Annunziata G, Colicchio Roberta, Greco Adelaide, Cerciello Raimondo, Auletta Luigi, Albanese Sandra, Scaglione Elena, Pagliarulo Caterina, Pastore Gabiria, Mansueto Gelsomina, Brunetti Arturo, Avallone Bice, Salvatore Paola
Department of Molecular Medicine and Medical Biotechnology, Federico II University Medical SchoolNaples, Italy; CEINGE-Advanced BiotechnologiesNaples, Italy.
Department of Molecular Medicine and Medical Biotechnology, Federico II University Medical School Naples, Italy.
Front Microbiol. 2016 Nov 7;7:1750. doi: 10.3389/fmicb.2016.01750. eCollection 2016.
is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that colonization is able to prevent damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of in immunocompromised hosts, SCID mice were co-infected with wild type or its mutant ΔPSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with and co-infected with ΔPSA presented the major echostructural alterations. Half of the mice infected with and all those co-infected with ΔPSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with ΔPSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with wild type while those infected with ΔPSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with and co-infected with ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations.
是一种革兰氏阴性兼性细胞内细菌,是猫抓病的病原体。我们之前的数据表明,在实验性小鼠模型中,该菌的定殖能够通过多糖A(PSA)预防损伤。为了确定PSA对于免疫功能低下宿主抵御该菌致病作用是否至关重要,将SCID小鼠与野生型或其突变体ΔPSA共同感染,并通过高频超声(HFUS)、组织病理学检查和透射电子显微镜(TEM)观察感染对小鼠组织的影响。首次在免疫功能低下的小鼠模型中分析了回声结构、肝叶长度、血管改变以及肝功能障碍的间接征象,这些征象在人类中通常用作疾病的标志。我们的研究结果显示,与磷酸盐缓冲溶液(PBS)对照组相比,所有感染小鼠均出现回声结构改变;此外,感染该菌和与ΔPSA共同感染的小鼠出现了主要的回声结构改变。与肾皮质相比,感染该菌的小鼠中有一半以及所有与ΔPSA共同感染的小鼠均表现出肝脏回声改变。与PBS对照组相比,与ΔPSA共同感染的小鼠的回声评分有显著差异(p < 0.05)。此外,组织病理学评估的炎症评分与超声检查结果相当一致。通过TEM进行的超微结构分析显示,感染野生型该菌的SCID小鼠肝脏样本无明显改变,而与PBS对照组相比,感染ΔPSA的小鼠主血管周围出现了胶原蛋白。感染该菌的小鼠肝脏样本显示有富含胶原蛋白、星状细胞和组织细胞的大区域。有趣的是,我们的数据表明,感染该菌并与ΔPSA共同感染的免疫功能低下的SCID小鼠表现出最严重的肝脏形态结构损伤。此外,这些结果表明,HFUS与组织病理学评估一起可被视为评估肝脏改变的良好影像学方法。