Plasmodium parasitophorous vacuole membrane-resident protein UIS4 manipulates host cell actin to avoid parasite elimination

M’Bana, Viriato; Lahree, Aparajita; Marques, Sofia; Slavic, Ksenija; Mota, Maria M.

doi:10.1016/j.isci.2022.104281

Cited by 8 publications

(3 citation statements)

References 38 publications

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“…However, they might be of clinical relevance as it has been suggested that liver injury in clinical malaria is an overlooked phenomenon 67 . We do not observe co-localization of IHSs with parasites stained with UIS4 antibodies, UIS4 has been ascribed a critical role in avoiding parasite elimination, suggesting the parasites we detect are still intact 68 . Immune infiltration could be triggered by the parasite's initial traversal through hepatocytes during early invasion, or by parasites that failed to successfully invade or develop early during the liver stage.…”

Section: Discussioncontrasting

confidence: 66%

Host-Pathogen Interactions in thePlasmodium-Infected Mouse Liver at Spatial and Single-Cell Resolution

Hildebrandt,

Urrutia-Iturritza,

Zwicker

et al. 2023

Preprint

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Upon infecting its vertebrate host, the malaria parasite initially invades the liver where it undergoes massive replication, whilst remaining clinically silent. The spatial coordination of factors regulating immune responses and metabolic zonation during malaria infection, in the true tissue context, remains unexplored. Here, we perform spatial transcriptomics in combination with single-nuclei RNA-sequencing (snRNA-seq) over multiple time points during liver infection to delineate transcriptional programs of host-pathogen interactions acrossP. berghei-infected liver tissues. Our data suggest changes in gene expression related to lipid metabolism in response toPlasmodiuminfection in the proximity of infected hepatocytes, such as the modulation of the expression of genes involved in peroxisome proliferator-activated receptor pathway signaling. The data further indicate the presence of inflammatory hotspots with distinct cell type compositions and differential liver inflammation programs along the lobular axis in the malaria-infected tissues. Furthermore, a significant upregulation of genes involved in inflammation is observed in liver tissues of control mice injected with mosquito salivary gland components, which is considerably delayed compared toP. bergheiinfected mice. Our study establishes a benchmark for investigating transcriptome changes during host-parasite interactions in tissues, it provides informative insights regardingin vivostudy design linked to infection, and provides a useful tool for the discovery and validation ofde novointervention strategies aimed at malaria liver stage infection.

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Section: Discussioncontrasting

confidence: 66%

Host-Pathogen Interactions in thePlasmodium-Infected Mouse Liver at Spatial and Single-Cell Resolution

Hildebrandt,

Urrutia-Iturritza,

Zwicker

et al. 2023

Preprint

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“…This membrane-enclosed structure helps the parasite to overcome its intracellular degradation while residing inside the host cells ( 31 ). A parasite-derived PVM-resident protein upregulated in infectious sporozoites 4 (UIS4), interacts with the host cell actin and by suppressing filamentous actin formation, UIS4 avoids parasite elimination ( 32 ). Hepatic Merozoites employ various immune evasion strategies to overcome the role of liver phagocytic cells in their development.…”

Section: Parasite Survival or Immune Evasion Strategies In Mammalian ...mentioning

confidence: 99%

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

et al. 2023

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Malaria is a global infectious disease that remains a leading cause of morbidity and mortality in the developing world. Multiple environmental and host and parasite factors govern the clinical outcomes of malaria. The host immune response against the Plasmodium parasite is heterogenous and stage-specific both in the human host and mosquito vector. The Plasmodium parasite virulence is predominantly associated with its ability to evade the host’s immune response. Despite the availability of drug-based therapies, Plasmodium parasites can acquire drug resistance due to high antigenic variations and allelic polymorphisms. The lack of licensed vaccines against Plasmodium infection necessitates the development of effective, safe and successful therapeutics. To design an effective vaccine, it is important to study the immune evasion strategies and stage-specific Plasmodium proteins, which are targets of the host immune response. This review provides an overview of the host immune defense mechanisms and parasite immune evasion strategies during Plasmodium infection. Furthermore, we also summarize and discuss the current progress in various anti-malarial vaccine approaches, along with antibody-based therapy involving monoclonal antibodies, and research advancements in host-directed therapy, which can together open new avenues for developing novel immunotherapies against malaria infection and transmission.

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“…To validate this coIP PbRab5b signal in infected HepG2 cells and to exclude other parasite components as putative mediators, a transfection system was employed. HEK-293T cells were transfected with four different constructs: (1) a construct expressing HA only, (2) expressing the cytosolic domain of PbUIS4_HA ($14 kDa, monomeric but runs around 27 kDa on PAGE) (M'Bana et al, 2021), (3) expressing PbRab5b_HA ($24 kDa), or (4) expressing the GTPase-deficient mutant-PbRab5b_Q91L_HA. These differently transfected cells were then subjected to APPL1 immunoprecipitation.…”

Section: Pbrab5b Engages Host Appl1 Independently Of Other Parasite C...mentioning

confidence: 99%

Active APPL1 sequestration by Plasmodium favors liver-stage development

et al. 2022

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Plasmodium parasitophorous vacuole membrane-resident protein UIS4 manipulates host cell actin to avoid parasite elimination

Cited by 8 publications

References 38 publications

Host-Pathogen Interactions in thePlasmodium-Infected Mouse Liver at Spatial and Single-Cell Resolution

Host-Pathogen Interactions in thePlasmodium-Infected Mouse Liver at Spatial and Single-Cell Resolution

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Active APPL1 sequestration by Plasmodium favors liver-stage development

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