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Active APPL1 sequestration by Plasmodium favors liver-stage development
Lahree, Aparajita; Baptista, Sara de Jesus Santos; Marques, Sofia; Perschin, Veronika; Zuzarte-Luis, Vanessa; Goel, Manisha; Choudhary, Hadi HasanIntracellular pathogens manipulate host cells to survive and thrive. Cellular sensing and signaling pathways are among the key host machineries deregulated to favor infection. In this study, we show that liver-stage Plasmodium parasites compete with the host to sequester a host endosomal-adaptor protein (APPL1) known to regulate signaling in response to endocytosis. The enrichment of APPL1 at the parasitophorou...
Academic labs supporting COVID‐19 diagnostics
Veldhoen, Marc; Zuzarte-Luis, VanessaDespite news about the new virus SARS-CoV-2 and COVID-19 grabbing the headlines in the beginning of 2020, life and work carried on as normal in most academic labs. Lab projects were the focus, results discussed face-to-face and hypothesis dismissed. Conferences were attended in person and flights to the next meeting often booked already. By March, the seriousness became clear. With surrounding countries reporti...
Acute invariant NKT cell activation triggers an immune response that drives pro...
Huang, Hua; Zuzarte-Luis, Vanessa; Fragoso, Gabriela; Calvé, Annie; Hoang, Tuan Anh; Oliero, Manon; Chabot-Roy, Geneviève; Mullins-Dansereau, VictorIron homeostasis is an essential biological process that ensures the tissue distribution of iron for various cellular processes. As the major producer of hepcidin, the liver is central to the regulation of iron metabolism. The liver is also home to many immune cells, which upon activation may greatly impact iron metabolism. Here, we focus on the role of invariant natural killer T (iNKT) cells, a subset of T lym...
Plasmodium translocon component EXP2 facilitates hepatocyte invasion
Mello-Vieira, Joao; Enguita, Francisco J.; De Koning-Ward, Tania; Zuzarte-Luis, Vanessa; Mota, Maria M.Plasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Protein 2 (EXP2) is critical for invasion of hepatocytes. EXP2 is ...
γδ-T cells promote IFN-γ–dependent Plasmodium pathogenesis upon liver-stage inf...
Ribot, Julie; Neres, Rita; Zuzarte-Luis, Vanessa; Gomes, Anita Q.; Mancio-Silva, Liliana; Mensurado, Sofia; Neves, Daniel; Monteiro Dos Santos, MiguelCerebral malaria (CM) is a major cause of death due to Plasmodium infection. Both parasite and host factors contribute to the onset of CM, but the precise cellular and molecular mechanisms that contribute to its pathogenesis remain poorly characterized. Unlike conventional αβ-T cells, previous studies on murine γδ-T cells failed to identify a nonredundant role for this T cell subset in experimental cerebral mal...
Parasite sensing of host nutrients and environmental cues
Zuzarte-Luis, Vanessa; Mota, Maria M.Parasites undergo complex life cycles that comprise a wide variety of cellular differentiation events in different host compartments and transmission across multiple hosts. As parasites depend on host resources, it is not surprising they have developed efficient mechanisms to sense alterations and adapt to the available resources in a wide range of environments. Here we provide an overview of the nutritional ne...
Unveiling the pathogen behind the vacuole
Liehl, Peter; Zuzarte-Luis, Vanessa; Mota, Maria M.Many clinically relevant pathogens, including certain bacteria and protozoan parasites, have developed an intracellular lifestyle that enables them to nestle in customized vacuoles. Although these pathogens are protected from extracellular defences, recent findings indicate that host cells have evolved multiple strategies to unmask the pathogen disguised by the vacuole and thereby initiate innate immune respons...
The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage ...
Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for developing next-generation antimalarial drugs. Using an integrated chemogenomics approach that combined drug resistance selection, whole-genome sequencing, and an orthogona...
Malaria infections: what and how can mice teach us
Zuzarte-Luis, Vanessa; Mota, Maria M.; Vigario, Ana MargaridaMalaria imposes a horrific public health burden - hundreds of millions of infections and millions of deaths - on large parts of the world. While this unacceptable health burden and its economic and social impact have made it a focal point of the international development agenda, it became consensual that malaria control or elimination will be difficult to attain prior to gain a better understanding of the compl...
Simple, sensitive and quantitative bioluminescence assay for determination of m...
Zuzarte-Luis, Vanessa; Sales Dias, Joana; Mota, Maria M.Background: The first phase of malaria infection occurs in the liver and is clinically silent. Inside hepatocytes each Plasmodium sporozoite replicate into thousands of erythrocyte-infectious merozoites that when released into the blood stream result in clinical symptoms of the disease. The time between sporozoite inoculation and the appearance of parasites in the blood is defined as the pre-patent period, whic...