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Immunopathology and Trypanosoma congolense parasite sequestration cause acute c...

De Niz, Mariana; Silva Pereira, Sara; Serre, Karine; Ouarné, Marie; Coelho, Joana E; Franco, Claudio; Figueiredo, Luisa M.

Trypanosoma congolense causes a syndrome of variable severity in animals in Africa. Cerebral trypanosomiasis is a severe form, but the mechanism underlying this severity remains unknown. We developed a mouse model of acute cerebral trypanosomiasis and characterized the cellular, behavioral, and physiological consequences of this infection. We show large parasite sequestration in the brain vasculature for long p...


Surgical and intravital microscopy protocol to image Trypanosoma brucei–host in...

De Niz, Mariana; Figueiredo, Luisa M.

Intravital microscopy (IVM) involves surgical procedures to expose the internal organs of live anesthetized animals to visualize fluorescently labeled components in situ, in vivo at subcellular resolution. Here, we provide an IVM protocol for time-lapse imaging of dynamic Trypanosoma brucei-host interactions in ten mammalian organs and in systemic circulation. We describe intraperitoneal or intradermal injectio...


Slow growing behavior in African trypanosomes during adipose tissue colonization

Trindade, Sandra; De Niz, Mariana; Sequeira, Mariana; Rebelo, Tiago; Bento, Fabio; Dejung, Mario; Narciso, Marta Valido; Escobar, Lara; Ferreira, João

When Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of prote...


N6-methyladenosine in poly(A) tails stabilize VSG transcripts

Viegas, Idálio; Macedo, Juan; Serra, Lúcia; De Niz, Mariana; Temporão, Adriana; Silva Pereira, Sara; Mirza, Aashiq H.; Bergstrom, Ed; Rodrigues, Joao A.

RNA modifications are important regulators of gene expression1. In Trypanosoma brucei, transcription is polycistronic and thus most regulation happens post-transcriptionally2. N6-methyladenosine (m6A) has been detected in this parasite, but its function remains unknown3. Here we found that m6A is enriched in 342 transcripts using RNA immunoprecipitation, with an enrichment in transcripts encoding variant surfac...


Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropi...

De Niz, Mariana; Brás, Daniela; Ouarné, Marie; Pedro, Mafalda; Nascimento, Ana M.; Henao Mišíková, Lenka; Franco, Claudio; Figueiredo, Luisa M.

Trypanosoma brucei is responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we observe that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show t...


Intravital imaging of host–parasite interactions in skin and adipose tissues

De Niz, Mariana; Meehan, Gavin R.; Brancucci, Nicolas M. B.; Marti, Matthias; Rotureau, Brice; Figueiredo, Luisa M.; Frischknecht, Friedrich

Intravital microscopy allows the visualisation of how pathogens interact with host cells and tissues in living animals in real time. This method has enabled key advances in our understanding of host-parasite interactions under physiological conditions. A combination of genetics, microscopy techniques, and image analysis have recently facilitated the understanding of biological phenomena in living animals at cel...


Toolbox for In Vivo imaging of host–parasite interactions at multiple scales

De Niz, Mariana; Spadin, Florentin; Marti, Matthias; Stein, Jens V.; Frenz, Martin; Frischknecht, Friedrich

Animal models have for long been pivotal for parasitology research. Over the last few years, techniques such as intravital, optoacoustic and magnetic resonance imaging, optical projection tomography, and selective plane illumination microscopy developed promising potential for gaining insights into host-pathogen interactions by allowing different visualization forms in vivo and ex vivo. Advances including incre...


Tissue tropism in parasitic diseases

Silva Pereira, Sara; Trindade, Sandra; De Niz, Mariana; Figueiredo, Luisa M.

Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries. Controlling these diseases requires a better understanding of host-parasite interactions, including a deep appreciation of parasite distribution in the host. The preferred accumulation of parasites in some tissues of the host ha...


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