Biology subjects

Danckaert, A.

Publications and source records attributed to Danckaert, A..

3 recordsLinked to original sources

bioRxiv2025

Intrinsic differences in hamster and mouse macrophage biology correlate with susceptibility to L. donovani infection

The basis for differential susceptibility to Leishmania (L.) donovani infection observed in individuals remains poorly understood. Here we address this important open question comparing bone marrow-derived macrophages from susceptible hamsters (hamBMDMs) and resistant mice (mBMDMs) to identify intrinsic cellular features that may contribute to host-specific outcomes. We first optimized and validated an experimental protocol for generating hamBMDMs, which closely resemble classical mouse BMDMs in terms of morphology, marker gene expression and phagocytic activity. Comparative transcriptomic analysis uncovered rodent-specific, intrinsic differences in the expression of metabolic and immune-related pathways known to influence susceptibility to intracellular Leishmania infection. In vitro infection assays confirmed the microbicidal capacity of hamBMDMs, while also revealing their increased permissiveness to Leishmania proliferation. In conclusion, the combined use of murine and hamster macrophage systems provides a powerful platform to dissect the molecular mechanisms underlying L. donovani survival and host resistance. Our improved protocol allows for the generation of large quantities of functionally validated hamster macrophages, enabling systems-level investigations in this important rodent model that more accurately reflects human infection dynamics than mice. This addresses a major bottleneck in experimental infections with L. donovani, but also other clinically relevant pathogens, such as Mycobacterium spp. and SARS-CoV-2, for which hamsters have been used to model human infection.

pathology↗

bioRxiv2023

An oxadiazole-based compound potentiates anti- tuberculosis treatment by increasing host resistance via zinc poisoning

Anti-tuberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains of Mycobacterium tuberculosis are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high content imaging, we identified novel 1,2,4-oxadiazole-based compounds, that allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, M. tuberculosis became even more sensitive to anti-tuberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

microbiology↗

bioRxiv2018

Imaging of red-shifted photons from bioluminescent tumours using fluorescence by unbound excitation from luminescence

Early detection of tumours is today a major challenge and requires sensitive imaging methodologies coupled with new efficient probes. Bioluminescence imaging has been widely used in the field of oncology and several cancer cell lines have been genetically modified to provide bioluminescence signals. However, photons that are emitted by the majority of commonly used luciferases are usually in the blue part of the visible spectrum, where tissue absorption is still very high, making deep tissue imaging non-optimal and calling for optimised optical imaging methodologies. We have previously shown that red-shifting of bioluminescence signal by Fluorescence Unbound Excitation from Luminescence (FUEL) is a mean to increase bioluminescence signal sensitivity detection in vivo. Here, we applied FUEL to tumour detection in two different subcutaneous tumour models: the auto-luminescent human embryonic kidney (HEK293) cell line and the murine B16-F10 melanoma cell line previously transfected with the plasmid Luc2. Tumour size and bioluminescence were measured over time and tumour vascularization characterized. We then locally injected near infrared emitting Quantum Dots (NIR QDs)in the tumour site and observed a red-shifting of bioluminescence signal by (FUEL) indicating that FUEL could be used to allow deeper tumour detection.

bioengineering↗