Impact of external stimuli on life cycle progression in the intestinal parasites Eimeria falciformis and Giardia duodenalis

Parasiten durchlaufen in ihrem Lebenszyklus morphologisch verschiedene Stadien. Die Kontrolle des Übergangs zwischen den Stadien kann die Transmission in einen neuen Wirt begünstigen. Bei vielen Parasiten ist unbekannt, welche Faktoren die Progression des Lebenszyklus beeinflussen. Der Ablauf kann genetisch prädeterminiert sein (kanalisiert) oder von äußeren Einflüssen abhängen (phänotypische Plastizität). Hier wurde die Progression des Lebenszyklus zweier Darmparasiten in Mäusen untersucht. Die Oozysten von Eimeria falciformis wurden quantifiziert und die Transkriptome von Parasit und Wirt wurden in Mäusen unterschiedlicher Immunkompetenz analysiert. Wenngleich erwartet wurde, dass die Immunantwort einen Stressor für das Pathogen darstellt, hatte die Immunkompetenz des Wirts keine Auswirkungen auf den Zeitpunkt der Oozystenausscheidung und das Transkriptomprofil des Parasiten. E. falciformis konnte nicht von der Immunschwäche des Wirtes profitieren; ist also hinsichtlich der Immunantwort des Wirts genetisch kanalisiert. In G. duodenalis wurde untersucht, inwiefern die Progression des Lebenszyklus, d.h die Trophozoitenreplikation bzw. die Zystenausscheidung, von Arginin abhängt. Die Replikation der Trophozoiten war nicht von Arginin aus der Nahrung abhängig; die Ausscheidung infektiöser Zysten war unter argininarmen Bedingungen jedoch verringert. Dies lässt vermuten, dass der Ablauf des Lebenszyklus von G. duodenalis, insbesondere die Enzystierung, an die Argininzufuhr gekoppelt ist. Die Umstellung des Metabolismus von G. duodenalis hin zur Produktion eines wichtigen Zystenwandbestandteils wird hier als mechanistische Verbindung zwischen ATP-Erzeugung aus Arginin in Nichtsäugetieren (Arginindihydrolase-Stoffwechselweg), verringerter Glykolyse und der Zystenwandsynthese erörtert. Somit könnte Arginin als Stimulus für phänotypische Plastizität bei der Enzystierung von G. duodenalis dienen.Eukaryotic parasites have life cycles with morphologically distinct stages. Accurate timing of the conversion from one stage into another can be beneficial for transmission into a new host. Often little is known about determinants for such life cycle progression or the genes involved. Timing can be genetically pre-determined (canalized) or depend on exposure to a stimulus (phenotypic plasticity). Here, life cycle progression of two unicellular intestinal parasites was investigated in mice. For Eimeria falciformis, oocyst stage parasites were quantified, and parasite and host transcriptomes analyzed in differently immune competent hosts. Host immune response stimuli are expected to induce stress on the pathogen, but different host immune competences did not change the timing of oocyst shedding or influence parasite transcriptome profiles. E. falciformis was unable to benefit from hosts with weakened immune responses. It is therefore an example of a genetically canalized parasite with regards to host immune stimulus. In Giardia duodenalis, dependence on arginine for life cycle progression was investigated. The in vivo relevance for parasite replication is unknown. Trophozoite stage replication and cyst shedding were assessed in hosts fed normal and arginine-free diets. G. duodenalis did not depend on dietary arginine for trophozoite replication, but infective cysts were reduced in number under arginine-poor conditions. Dependence on arginine for life stage switching suggests that G. duodenalis could time progression by encysting upon arginine exposure. G. duodenalis metabolic reprograming to generate a major cyst wall component is discussed as a strategy to mechanistically link 1) non-mammalian ATP generation (arginine dihydrolase pathway) from arginine with 2) decreased glycolytic flux and 3) cyst wall generation. Therefore, arginine may be an external stimulus for phenotypic plasticity of encystation in G. duodenalis

Adult Neurogenesis of the Medial Geniculate Body: In Vitro and Molecular Genetic Analyses Reflect the Neural Stem Cell Capacity of the Rat Auditory Thalamus over Time

Neural stem cells (NSCs) have been recently identified in the neonatal rat medial geniculate body (MGB). NSCs are characterized by three cardinal features: mitotic self-renewal, formation of progenitors, and differentiation into all neuroectodermal cell lineages. NSCs and the molecular factors affecting them are particularly interesting, as they present a potential target for treating neurologically based hearing disorders. It is unclear whether an NSC niche exists in the rat MGB up to the adult stage and which neurogenic factors are essential during maturation. The rat MGB was examined on postnatal days 8, 12, and 16, and at the adult stadium. The cardinal features of NSCs were detected in MGB cells of all age groups examined by neurosphere, passage, and differentiation assays. In addition, real-time quantitative polymerase chain reaction arrays were used to compare the mRNA levels of 84 genes relevant to NSCs and neurogenesis. In summary, cells of the MGB display the cardinal features of NSCs up to the adult stage with a decreasing NSC potential over time. Neurogenic factors with high importance for MGB neurogenesis were identified on the mRNA level. These findings should contribute to a better understanding of MGB neurogenesis and its regenerative capacity

Characterization of a Human Respiratory Mucosa Model to Study Odorant Metabolism

Corresponding author: [email protected] audienceNasal xenobiotic metabolizing enzymes (XMEs) are important for the sense of smell because they influence odorant availability and quality. Since the major part of the human nasal cavity is lined by a respiratory mucosa, we hypothesized that this tissue contributed to nasal odorant metabolism through XME activity. Thus, we built human respiratory tissue models and characterized the XME profiles using single-cell RNA sequencing. We focused on the XMEs dicarbonyl and l-xylulose reductase, aldehyde dehydrogenase (ALDH) 1A1, and ALDH3A1, which play a role in food odorant metabolism. We demonstrated protein abundance and localization in the tissue models and showed the metabolic activity of the corresponding enzyme families by exposing the models to the odorants 3,4-hexandione and benzaldehyde. Using gas chromatography coupled with mass spectrometry, we observed, for example, a significantly higher formation of the corresponding metabolites 4-hydroxy-3-hexanone (39.03 ± 1.5%, p = 0.0022), benzyl alcohol (10.05 ± 0.88%, p = 0.0008), and benzoic acid (8.49 ± 0.57%, p = 0.0004) in odorant-treated tissue models compared to untreated controls (0 ± 0, 0.12 ± 0.12, and 0.18 ± 0.18%, respectively). This is the first study that reveals the XME profile of tissue-engineered human respiratory mucosa models and demonstrates their suitability to study nasal odorant metabolism