30th Annual Meeting of the German Society for Parasitology

Prof. Dr.

Host immune effects on Echinococcus multilocularis developmental transitions

Abstract text Introduction: The lethal zoonosis alveolar echinococcosis is caused by tumor-like growth of the metacestode larva of the tapeworm Echinococcus multilocularis within host organs. We previously established that the formation of the unusual metacestode is accompanied by drastic modifications of the parasite&quot;s body axes. First, the anterior pole of the invading oncosphere is shut down within the host, resulting in the posteriorized, invasively growing metacestode. Later during an infection, the anterior pole is re-established which subsequently leads to the formation of numerous protoscoleces. How these modifications are regulated is unclear. Objectives: To investigate host influences on parasite developmental transitions and to characterize associated parasite signaling pathways. Materials &amp; methods: We used parasite in vitro cultivation systems to study the influence of host cytokines on parasite development and differentiation, coupled with in situ hybridization and functional assays on parasite receptor systems. Results: We show that the formation of metacestode vesicles from parasite stem cells is significantly stimulated by physiological conditions of TNF-alpha, which is produced early during Echinococcus infections, by direct activation of a metacestode-specifically expressed TNF-alpha receptor through the host cytokine. We also show that TGF-beta, which accumulates around the metacestode during late stages of the infection, can directly stimulate Echinococcus TGF-receptors and induces the formation of brood capsules and protoscoleces in mature metacestode vesicles. Small molecule inhibitors against the parasite&quot;s TGF-beta-receptors, on the other hand, blocked the formation of brood capsules and protoscoleces in otherwise unaffected, mature metacestode vesicles. Conclusions: Our data indicate that the Echinococcus-specific modulation of body axes which results in the formation of the metacestode is directly influenced by host cytokines that are formed during different phases of the immune response against the parasite. As such, the potentially parasitocidal, Th1-dominated immune response early during an infection fosters invasive parasite growth, whereas increased immune suppression around the parasitic lesions during late infections physiologically prepares E. multilcularis for the transmission to the next (definitive) host.

Molecular Parasitology

Parasite-Host Interaction

Talk

A decade of research on neurotoxocarosis – an overview on tropisms, pathomechanisms, transcriptomics and lipidomics associated with neuroinvasive Toxocara larvae

Abstract text Neuroinvasive third-stage larvae (neural larva migrans, NLM) of Toxocara canis or Toxocara cati may lead to severe neurological symptoms in paratenic hosts, known as neurotoxocarosis (NT). To improve the understanding of Toxocara-induced neuropathology, several studies focused on the investigation of NLM in the mouse as the most appropriate model organism for NT. In the past decade, several defined aspects of NLM were unravelled such as the differential neurotropism of T. canis and T. cati, Toxocara-mediated neuronal demyelination, neurobehavioural as well as memory function deficits and pathological, transcriptional as well as lipidomic changes in infected mice. All of these mentioned studies were performed under similar conditions, including the same mouse and parasite strains, infective doses and examination time points, making these data suitable for comparative meta-analysis. Initial results showed correlations between memory impairment, larval recovery, microglia activation, β-amyloid precursor protein accumulation and demyelination of infected mice. Moreover, an extended meta-analysis including differentially transcribed genes and immunomodulatory mediators will aid in elucidating whether Toxocara-mediated neurodegenerative processes are a cause of neurological and behavioural impairments. In conclusion, this meta-analysis will provide a holistic and comprehensive overview on and unravel the relation between above-mentioned features of neurotoxocarosis.

Soil-transmitted Parasitoses

Univ.-Prof. Dr. rer. nat.

Ascaris suum interacts with host microbes and acquires its own microbiome

Abstract text Introduction Ascariasis is amongst the most prevalent soil-transmitted helminth infections in humans and pigs. In addition to modulating the host immune system, Ascaris resides in the microbial environment of the intestine and Ascaris infections are associated with alterations in the host microbiome. Additionally, Ascaris possesses its own intestine from which bacteria can be cultured. Despite the close association between intestinal nematodes and microbes, little is currently known about how nematodes contend with, or benefit from, their microbial neighbors and even less is known about the parasite&quot;s own microbiome. Objectives The objectives of this work were to characterize antimicrobial strategies of helminths and to understand the elucidate the parasite microbiome and its interplay with the microbiome of its host. Materials &amp; Methods Antimicrobial activities were assessed by harvesting excreted and secreted products (ESPs) of Ascaris suum and employing ESPs in various antimicrobial assays. Furthermore, ESPs were assessed by mass spectrometry. The Ascaris microbiome and the microbiome of its host were assessed by sequencing of the 16S rRNA gene in samples obtained from infected pigs. Results A. suum ESPs were found to possess various components with known and predicted antimicrobial activities. These products also reduced bacterial growth and disrupted biofilm formation in vitro. Furthermore, ESPs were also found to agglutinate bacteria. The A. suum microbiome was found to be derived, but distinct from, the microbiome of its host. In particular, dominant bacteria present at the site of infection appear to drive microbiome composition of the worm. Conclusion Our work presents a first look at the parasite microbiome while elucidating different antimicrobial strategies of Ascaris worms. These findings suggest that A. suum may selectively acquire microbes from their immediate surroundings.

Prof.

Identification of GPCR-neuropeptide interactions and their functional analyses in Schistosoma mansoni

Abstract text Introduction Schistosomes are parasitic flatworms that cause schistosomiasis. Standard treatment of schistosomiasis relies on a single drug, praziquantel. Neuropeptides are important messenger molecules that act via G protein-coupled receptors (GPCRs) as neurotransmitters, or hormones in the nervous system. Due to their pharmacological importance and proven druggability, GPCRs represent promising targets for new anthelmintics. Comparative transcriptomics of paired and unpaired worms and their gonads revealed 59 differentially regulated GPCR genes putatively involved in Schistosoma mansoni neuronal processes. Furthermore, 23 of 27 S. mansoni neuropeptide precursor (Sm_npp) genes of adult S. mansoni exhibited higher transcript levels in males (paired or unpaired) and unpaired females. Objectives Our knowledge of S. mansoni GPCRs and their ligands are still fragmentary. Goal of this study was to confirm rhodopsin-like orphan GPCR (SmGPCR20)-Sm_npp interactions by biochemical methods and to characterize the appropriate partners at the molecular level including functional analyses. Materials &amp; methods To characterize SmGPCR20, we employed the MALAR-Y2H system. We examined the transcript profiles by quantitative real-time PCR (qRT-PCR) and localized their transcripts by whole mount in situ hybridization (WISH). To unravel the function of the receptor/ligand pairs, we performed RNA interference (RNAi) in adult S. mansoni in vitro with subsequent phenotype analysis. Confocal laser scanning microscopy (CLSM) was used for morphological analyses. Results We identified specific interactions between SmGPCR20/SmNPP26 and SmGPCR20/SmNPP40 and co-localized SmGPCR20/SmNPP26 and SmGPCR20/SmNPP40 expression in the head region and along the worm body in particular patterns. SmGPCR20, SmNPP26, and SmNPP40 were found to be preferentially transcribed in bM and sM but also in sF. Phenotype analyses following RNAi against these molecules indicated a substantial decline in egg production compared with the untreated control group. Consistent with the decreased egg production, CLSM analyses revealed morphologic changes in the female gonads. Conclusion The obtained results suggest that SmNPP26 and SmNPP40 are ligands of SmGPCR20, and that these molecules are involved in the molecular communication of male and female S. mansoni influencing egg production. Furthermore, GPCRs and neuropeptides may play important roles for male-female interaction and the control of reproduction.

Session XII
Parasite-Host-Interactions II – Cestoda/Trematoda/Nematoda

Termin

Vorsitzende

Programm

Session XIIParasite-Host-Interactions II – Cestoda/Trematoda/Nematoda

Termin

Vorsitzende

Programm

Session XII
Parasite-Host-Interactions II – Cestoda/Trematoda/Nematoda