Mycobacterium tuberculosis, the agent of TB, is one of the deadliest human pathogens, infecting one third of the global population. Establishment of infection by mycobacteria relies on complex... Show moreMycobacterium tuberculosis, the agent of TB, is one of the deadliest human pathogens, infecting one third of the global population. Establishment of infection by mycobacteria relies on complex interactions with host innate immune cells, especially macrophages. Once engulfed by macrophages, mycobacteria “usurp” the host cell machineries to facilitate dissemination and to establish an intracellular niche for survival and replication. To investigate how mycobacteria force the immune cells to support infection, we explored the chemokine pathway, best known for its capability to induce cell migration. To dissect the interplay between immune cells and the pathogen, we modelled human TB using the zebrafish-Mycobacterium marinum natural host-pathogen pair, which is attractive for the excellent optical accessibility of the zebrafish larvae and the possibility to apply genetic tools to impair the chemokine signaling. We show that depletion of either CXCR3 or CXCR4 axes are beneficial to the host. Exploitation of CXCR3 signaling leads to macrophage recruitment and to transcriptional changes in macrophages that make them more permissive for mycobacterial intracellular persistence. Activating CXCR4 signaling triggers instead vascularization of the nascent tuberculous granulomas, which in turn supports expansion of the infection. Therefore, inhibitions of these pathways represent promising host-directed therapeutic avenues to counteract mycobacterial diseases. Show less
Aquatic and terrestrial habitats are heterogeneous by nature with respect to sound and light conditions. Fish may extract signals and exploit cues from both ambient modalities and they may also... Show moreAquatic and terrestrial habitats are heterogeneous by nature with respect to sound and light conditions. Fish may extract signals and exploit cues from both ambient modalities and they may also select their sound and light level of preference in free-ranging conditions. In recent decades, human activities in or near water have altered natural soundscapes and caused nocturnal light pollution to become more widespread. Artificial sound and light may cause anxiety, deterrence, disturbance or masking, but few studies have addressed in any detail how fishes respond to spatial variation in these two modalities. Here we investigated whether sound and light affected spatial distribution and swimming behavior of individual zebrafish that had a choice between two fish tanks: a treatment tank and a quiet and light escape tank. The treatments concerned a 2 × 2 design with noisy or quiet conditions and dim or bright light. Sound and light treatments did not induce spatial preferences for the treatment or escape tank, but caused various behavioral changes in both spatial distribution and swimming behavior within the treatment tank. Sound exposure led to more freezing and less time spent near the active speaker. Dim light conditions led to a lower number of crossings, more time spent in the upper layer and less time spent close to the tube for crossing. No interactions were found between sound and light conditions. This study highlights the potential relevance for studying multiple modalities when investigating fish behavior and further studies are needed to investigate whether similar patterns can be found for fish behavior in free-ranging conditions. Show less
Over the past few decades, public attention, activities in the field of conservation and animal welfare by nongovernmental organizations (NGOs), and scientific exploration are raising awareness on... Show moreOver the past few decades, public attention, activities in the field of conservation and animal welfare by nongovernmental organizations (NGOs), and scientific exploration are raising awareness on the potential effects of sounds on marine mammals and fish species. The aim of this thesis was to explore sound-induced behavioral changes in fish using captive zebrafish as a model species. I explored behavioural parameters as potential indicators of sound-related stress, disturbance and deterrence. In four different studies, I examined various sound exposure treatments to provide insights that may be useful for future explorations for indoor and outdoor sound impact studies as well as for assessing animal welfare and productivity in captive situations. Furthermore, my findings may also raise awareness for sound levels in laboratories and the potential effect on reliability for fish as a model species for medical and pharmaceutical studies. I also explored the complexity of sound fields in indoor fish tanks by selecting a different set-up for each study, which makes behavioural analyses and direct comparisons not only relevant within each study, but also provides insight into the role of fish tank acoustics on 'natural' and experimental exposure condition. Show less
Ent, W. van der; Veneman, W.J.; Groenewoud, A.; Chen, L.P.; Tulotta, C.; Hogendoorn, P.C.W.; ... ; Langenau, D.M. 2016
Zebrafish embryos can be obtained for research purposes in large numbers at low cost and embryos develop externally in limited space, making them highly suitable for high-throughput cancer studies... Show moreZebrafish embryos can be obtained for research purposes in large numbers at low cost and embryos develop externally in limited space, making them highly suitable for high-throughput cancer studies and drug screens. Non-invasive live imaging of various processes within the larvae is possible due to their transparency during development, and a multitude of available fluorescent transgenic reporter lines. To perform high-throughput studies, handling large amounts of embryos and larvae is required. With such high number of individuals, even minute tasks may become time-consuming and arduous. In this chapter, an overview is given of the developments in the automation of various steps of large scale zebrafish cancer research for discovering important cancer pathways and drugs for the treatment of human disease. The focus lies on various tools developed for cancer cell implantation, embryo handling and sorting, microfluidic systems for imaging and drug treatment, and image acquisition and analysis. Examples will be given of employment of these technologies within the fields of toxicology research and cancer research. Show less
