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Within the Enceladus Explorer Initiative of the DLR Space Administration navigation technologies for a future space mission are in development. Those technologies are the basis for the search for extraterrestrial life on the Saturn moon Enceladus. An autonomous melting probe, the EnEx probe, aims to extract a liquid sample from a water reservoir below the icy crust. A first EnEx probe was developed and demonstrated in a terrestrial scenario at the Bloodfalls, Taylor Glacier, Antarctica in November 2014. To enable navigation in glacier ice two acoustic systems were integrated into the probe in addition to conventional navigation technologies. The first acoustic system determines the position of the probe during the run based on propagation times of acoustic signals from emitters at reference positions at the glacier surface to receivers in the probe. The second system provides information about the forefield of the probe. It is based on sonographic principles with phased array technology integrated in the probe’s melting head. Information about obstacles or sampling regions in the probe’s forefield can be acquired. The development of both systems is now continued in the project EnEx-RANGE. The emitters of the localization system are replaced by a network of intelligent acoustic enabled melting probes. These localize each other by means of acoustic signals and create the reference system for the EnEx probe. This presentation includes the discussion of the intelligent acoustic network, the acoustic navigation systems of the EnEx probe and results of terrestrial tests.

Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS induced maturation of DCs and reprograms DCs toward a tolerance promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature [DCSIGN.sup.+]HLAD [R.sup.hi] CD [80.sup.lo] CD [86.sup.lo] phenotype. Mechanistically, the tolerogenic activity of H. pylori experienced DCs was shown to require IL-18 in vitro and in vivo; DC derived IL18 acted directly on T cells to drive their conversion to Tregs. [CD4.sup.+] [CD25.sup.+] Tregs from infected wild type mice but not [Il18.sup.-/-] or [Il18r1.sup.-/-] mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL18., Introduction DCs are predominantly known for their function as potent inducers of adaptive immunity. However, there is now increasing evidence that certain populations of poorly immunogenic DCs initiate and maintain [...]

Atopic asthma is a chronic disease of the airways that has taken on epidemic proportions in the industrialized world. The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies. In this study, we have utilized mouse models of allergic airway disease induced by ovalbumin or house dust mite allergen to experimentally examine a possible inverse correlation between H. pylori and asthma. H. pylori infection efficiently protected mice from airway hyperresponsiveness, tissue inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and prevented allergen-induced pulmonary and bronchoalveolar infiltration with eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust in mice infected neonatally and was abrogated by antibiotic eradication of H. pylori. Asthma protection was further associated with impaired maturation of lung-infiltrating dendritic cells and the accumulation of highly suppressive Tregs in the lungs. Systemic Treg depletion abolished asthma protection; conversely, the adoptive transfer of purified Treg populations was sufficient to transfer protection from infected donor mice to uninfected recipients. Our results thus provide experimental evidence for a beneficial effect of H. pylori colonization on the development of allergen-induced asthma., Introduction Atopic asthma is characterized by lung inflammation, airway hyper-responsiveness, and airway obstruction (1). The pulmonary infiltrates of asthmatic patients consist of eosinophils, mast cells, and activated Th2 and Th17 [...]

Despite a broad cell-type tropism, cytomegalovirus (CMV) is an evidentially pulmonary pathogen. Predilection for the lungs is of medical relevance in immunocompromised recipients of hematopoietic cell transplantation, in whom interstitial CMV pneumonia is a frequent and, if left untreated, fatal clinical manifestation of human CMV infection. A conceivable contribution of CMV to airway diseases of other etiology is an issue that so far attracted little medical attention. As the route of primary CMV infection upon host-to-host transmission in early childhood involves airway mucosa, coincidence of CMV airway infection and exposure to airborne environmental antigens is almost unavoidable. For investigating possible consequences of such a coincidence, we established a mouse model of airway co-exposure to CMV and ovalbumin (OVA) representing a protein antigen of an inherently low allergenic potential. Accordingly, intratracheal OVA exposure alone failed to sensitize for allergic airway disease (AAD) upon OVA aerosol challenge. In contrast, airway infection at the time of OVA sensitization predisposed for AAD that was characterized by airway inflammation, IgE secretion, thickening of airway epithelia, and goblet cell hyperplasia. This AAD histopathology was associated with a T helper type 2 (Th2) transcription profile in the lungs, including IL-4, IL-5, IL-9, and IL-25, known inducers of Th2-driven AAD. These symptoms were all prevented by a pre-challenge depletion of CD4+ T cells, but not of CD8+ T cells. As to the underlying mechanism, murine CMV activated migratory CD11b+ as well as CD103+ conventional dendritic cells (cDCs), which have been associated with Th2 cytokine-driven AAD and with antigen cross-presentation, respectively. This resulted in an enhanced OVA uptake and recruitment of the OVA-laden cDCs selectively to the draining tracheal lymph nodes for antigen presentation. We thus propose that CMV, through activation of migratory cDCs in the airway mucosa, can enhance the allergenic potential of otherwise poorly allergenic environmental protein antigens. [ABSTRACT FROM AUTHOR]

Summary: Background: The prevalence of asthma and chronic obstructive pulmonary disease (COPD) has risen markedly over the last decades and is reaching epidemic proportions. However, underlying molecular mechanisms are not fully understood, hampering the urgently needed development of approaches to prevent these diseases. It is well established from epidemiological studies that prenatal exposure to cigarette smoke is one of the main risk factors for aberrant lung function development or reduced fetal growth, but also for the development of asthma and possibly COPD later in life. Of note, recent evidence suggests that the disease risk can be transferred across generations, that is, from grandparents to their grandchildren. While initial studies in mouse models on in utero smoke exposure have provided important mechanistic insights, there are still knowledge gaps that need to be filled. Objective: Thus, in this review, we summarize current knowledge on this topic derived from mouse models, while also introducing two other relevant animal models: the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. Methods: This review is based on an intensive review of PubMed‐listed transgenerational animal studies from 1902 to 2018 and focuses in detail on selected literature due to space limitations. Results: This review gives a comprehensive overview of mechanistic insights obtained in studies with the three species, while highlighting the remaining knowledge gaps. We will further discuss potential (dis)advantages of all three animal models. Conclusion/Clinical Relevance: Many studies have already addressed transgenerational inheritance of disease risk in mouse, zebrafish or fly models. We here propose a novel strategy for how these three model organisms can be synergistically combined to achieve a more detailed understanding of in utero cigarette smoke‐induced transgenerational inheritance of disease risk. [ABSTRACT FROM AUTHOR]