multilocularis is able to use lipids as a source for carbon and energy. Although it is clear that glycolysis and tricarboxylic acid cycle are functional (yielding succinate under anaerobic conditions), results concerning lipid catabolism via beta-oxidation are lacking [67]. Host lipids may also be attracted and www.selleckchem.com/products/tofacitinib-cp-690550.html exposed as a part of a strategy to circumvent the host immune system. In any case, these proteins could be interesting targets to address in future studies, presently these molecules remain still at a speculative level and are difficult to discuss without further pathological characteristics related to these molecules. At a late stage of infection, fibrosis becomes a hallmark of AE, leading to a complete disappearance of the liver parenchyma and even to the death of the metacestode, with vesicles embedded in an acellular tissue composed nearly entirely of cross-linked collagens [68].
The diffusion of the fibrotic process even far from the parasitic lesions strongly suggests a major role for cytokines in collagen synthesis. But these features could not be addressed and thus also not discussed in the present study. As mentioned above, we will design new studies respecting temporal aspects to unravel late stage characteristics of murine AE. Conclusion The conventional course of AE as a disease in humans resembles strongly that of the naturally infected mouse, in that untreated AE will, in many but not most cases, finally lead to fatality. In order to better understand periparasitic events characterizing the host response to infection, we assessed the gene expression profile in the periparasitic liver tissue during early chronic AE.
High throughput analysis of gene expression yielded a set of mostly immunologically related upregulated genes, while downregulation almost exclusively lacked. The data presented herein may provide a road map for further investigations into the pathophysiology of AE and may help to identify potential targets for adjuvant therapy of this disease. Future interest will also focus on unraveling similar events but at late stage infection. Methods Model of alveolar echinococcosis An established mouse model of primary alveolar echinococcosis was used as previously described [3], [69]. The animal studies were approved by the Animal Care and Experimentation Committee of the Canton of Bern, Switzerland, and followed National Institutes of Health guidelines for the performance of animal experiments.
Briefly, 8-weeks-old female C57BL6/J mice were purchased from Charles River GmbH (Germany), and infected (n=10) at the age of 10 weeks by peroral inoculation with 100 ��l sterile water containing 2��103 eggs of E. multilocularis, using appropriate biosafety level 3 laboratory conditions (Swiss biosafety approval number A990006/3A). The infecting organisms (parasite eggs) were Batimastat initially isolated from a naturally infected fox.