Transforming growth factor-ß signalling regulates protoscolex formation in the Echinococcus multilocularis metacestode.

The lethal zoonosis alveolar echinococcosis (AE) is caused by tumor-like, infiltrative growth of the metacestode larval stage of the tapeworm Echinococcus multilocularis. We previously showed that the metacestode is composed of posteriorized tissue and that the production of the subsequent larval stage, the protoscolex, depends on re-establishment of anterior identities within the metacestode germinative layer. It is, however, unclear so far how protoscolex differentiation in Echinococcus is regulated. We herein characterized the full complement of E. multilocularis TGFß/BMP receptors, which is composed of one type II and three type I receptor serine/threonine kinases. Functional analyzes showed that all Echinococcus TGFß/BMP receptors are enzymatically active and respond to host derived TGFß/BMP ligands for activating downstream Smad transcription factors. In situ hybridization experiments demonstrated that the Echinococcus TGFß/BMP receptors are mainly expressed by nerve and muscle cells within the germinative layer and in developing brood capsules. Interestingly, the production of brood capsules, which later give rise to protoscoleces, was strongly suppressed in the presence of inhibitors directed against TGFß/BMP receptors, whereas protoscolex differentiation was accelerated in response to host BMP2 and TGFß. Apart from being responsive to host TGFß/BMP ligands, protoscolex production also correlated with the expression of a parasite-derived TGFß-like ligand, EmACT, which is expressed in early brood capsules and which is strongly expressed in anterior domains during protoscolex development. Taken together, these data indicate an important role of TGFß/BMP signalling in Echinococcus anterior pole formation and protoscolex development. Since TGFß is accumulating around metacestode lesions at later stages of the infection, the host immune response could thus serve as a signal by which the parasite senses the time point at which protoscoleces must be produced. Overall, our data shed new light on molecular mechanisms of host-parasite interaction during AE and are relevant for the development of novel treatment strategies.

Development of a point-of-care-device for fast detection of periodontal pathogens.

BACKGROUND: A number of pathogens can cause severe destruction of the periodontal apparatus during the course of periodontitis. The aim of this work was the development of a diagnostic device for the use at the point-of-need for the detection of periodontal pathogens to enable a personalized therapy for treatment of periodontitis. METHODS: This test system is based on the polymerase chain reaction of DNA isolated from periodontal pathogens and was examined to precisely detect species-specific sequences on a rotating chip with lyophilized reagents for polymerase chain reaction. The preservation of the reagents was optimized to ensure their stability during the storage. RESULTS: In the current work, we have developed a model point-of-care device and showed a proof of concept. It requires low sample volume, is timesaving and can therefore facilitate early diagnosis and treatment of periodontal diseases. CONCLUSIONS: The developed device can provide fast diagnosis of the composition and amount of patients' oral flora and might help to assess the stage of periodontitis infection. This can facilitate an optimization of therapeutic approaches in order to prevent some of the more serious consequences of the disease.