Shedding of host autophagic proteins from the parasitophorous vacuolar membrane of Plasmodium berghei

The hepatic stage of the malaria parasite Plasmodium is accompanied by an autophagy-mediated host response directly targeting the parasitophorous vacuolar membrane (PVM) harbouring the parasite. Removal of the PVM-associated autophagic proteins such as ubiquitin, p62, and LC3 correlates with parasite survival. Yet, it is unclear how Plasmodium avoids the deleterious effects of selective autophagy. Here we show that parasites trap host autophagic factors in the tubovesicular network (TVN), an expansion of the PVM into the host cytoplasm. In proliferating parasites, PVM-associated LC3 becomes immediately redirected into the TVN, where it accumulates distally from the parasite's replicative centre. Finally, the host factors are shed as vesicles into the host cytoplasm. This strategy may enable the parasite to balance the benefits of the enhanced host catabolic activity with the risk of being eliminated by the cell's cytosolic immune defence

Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration

Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three Trypanosoma species: T. brucei, T. congolense and T. vivax with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, T. congolense is strictly intravascular, while T. brucei is capable of surviving both extra- and intravascularly. Our knowledge regarding T. vivax tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that T. vivax parasites sequester to the vascular endothelium of most organs, and that, like T. congolense, T. vivax Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolense and T. vivax) and the non-sequestering, but extravasating, T. brucei raise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.info:eu-repo/semantics/publishedVersio

Intravital microscopy: imaging host‐parasite interactions in lymphoid organs

Intravital microscopy allows imaging of biological phenomena within living animals, including host‐parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host –parasite interactions within organs at depths, speeds, and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarize technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen, and the mucosa‐associated lymphoid tissue, and present a view into possible future applications

Toolbox for in vivo imaging of host-parasite interactions at multiple scales

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 increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods, facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold promising potential for the field of parasitology

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Paving the Way:Contributions of Big Data to Apicomplexan and Kinetoplastid Research

In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania biology. We debate the benefits and limitations of the current technologies, and propose future advancements that may be key to improving our use of these techniques. Finally, we consider the difficulties the field faces when trying to make the most of the abundance of data that has already been, and will continue to be, generated

Tissue tropism in parasitic diseases

© 2019 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.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 has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms. The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome. Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.L.M.F. is an Investigator of the Fundação para a Ciência e Tecnologia (IF/01050/2014) and the laboratory is funded by ERC (FatTryp, ref. 771714). M.D.N. is funded by Long Term EMBO Postdoctoral fellowship ALTF 1048-2016. Publication of this work was also funded by UID/BIM/50005/2019, from Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado.info:eu-repo/semantics/publishedVersio

Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis

© 2022, Silva Pereira, De Niz et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.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 periods of time (up to 8 hr) and extensive neuropathology that associate with ICAM1-mediated recruitment and accumulation of T cells in the brain parenchyma. Antibody-mediated ICAM1 blocking and lymphocyte absence reduce parasite sequestration in the brain and prevent the onset of cerebral trypanosomiasis. Here, we establish a mouse model of acute cerebral trypanosomiasis and we propose a mechanism whereby parasite sequestration, host ICAM1, and CD4+ T cells play a pivotal role.This work was supported by European Union’s Horizon 2020 research and innovation program through a Marie Skłodowska-Curie Individual Standard European Fellowship to S.S.P., under grant agreement no. 839960, and from the European Research Council (ERC) (FatTryp, 771714) to L.M.F. M.D.N. was funded by Human Frontiers LT000047/2019 L (HFSP) and EMBO (ALTF 1048–2016). L.M.F., K.S., and C.A.F. are Investigators CEEC of the Fundação para a Ciência e a Tecnologia (CEECIND/03322/2018, CEECIND/00697/2018, CEECIND/04251/2017, respectively). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Fundação para a Ciência e a Tecnologia (grants IF/00412/2012, EXPL/BEX- BCM/2258/2013, PRECISE-LISBOA-01–0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017).info:eu-repo/semantics/publishedVersio

Toolbox for in vivo imaging of host–parasite interactions at multiple scales

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 increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods, facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold promising potential for the field of parasitology

Developing a xenograft model of human vasculature in the mouse ear pinna

Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies