ArticleProceedings of the National Academy of Sciences of the United States of America2016
LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malaria Plasmodium vivax liver stage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- Hepatocyte Autophagy in Malaria: Current Concepts, Emerging Mechanisms, and Future Therapeutic Directions.Pathogens (Basel, Switzerland) · 2026Review
- Elimination of intra-hepatocytic malaria parasites is driven by non-canonical autophagy but not nitric oxide production.iScience · 2025Article
- IFN-γ-Driven macrophage responses in the immunity toFrontiers in cellular and infection microbiology · 2025Review
- Article
- Human liver organoids are susceptible to Plasmodium vivax infection.Malaria journal · 2024Article
- Hepatocytes and the art of killing Plasmodium softly.Trends in parasitology · 2024Review
- Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin.Malaria journal · 2024Article
- Interferon-Science (New York, N.Y.) · 2024Review
- Escaping the enemy's bullets: an update on how malaria parasites evade host immune response.Parasitology research · 2023Review
- Same, same but different: Exploring Plasmodium cell division during liver stage development.PLoS pathogens · 2023Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Overexpression of hepatocyte EphA2 enhances liver-stage infection by Plasmodium vivax.Scientific reports · 2022Article
- Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis.Science advances · 2022Review
- In vitro models for human malaria: targeting the liver stage.Trends in parasitology · 2022Review
- A single-cell liver atlas of Plasmodium vivax infection.Cell host & microbe · 2022Article
- Plasmodium's fight for survival: escaping elimination while acquiring nutrients.Trends in parasitology · 2022Review
- Autophagy Pathways in the Genesis ofLife (Basel, Switzerland) · 2022Article
- Innate immunity to malaria: The good, the bad and the unknown.Frontiers in immunology · 2022Review
- ATG Ubiquitination Is Required for Circumsporozoite Protein to Subvert Host Innate Immunity Against Rodent Malaria Liver Stage.Frontiers in immunology · 2022Article
- Host-targeted Interventions as an Exciting Opportunity to Combat Malaria.Chemical reviews · 2021Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IFN-γ is a major regulator of immune functions and has been shown to induce liver-stage Plasmodium elimination both in vitro and in vivo. The molecular mechanism responsible for the restriction of liver-stage Plasmodium downstream of IFN-γ remains uncertain, however. Autophagy, a newly described immune defense mechanism, was recently identified as a downstream pathway activated in response to IFN-γ in the control of intracellular infections. We thus hypothesized that the killing of liver-stage malarial parasites by IFN-γ involves autophagy induction. Our results show that whereas IFN-γ treatment of human hepatocytes activates autophagy, the IFN-γ-mediated restriction of liver-stage Plasmodium vivax depends only on the downstream autophagy-related proteins Beclin 1, PI3K, and ATG5, but not on the upstream autophagy-initiating protein ULK1. In addition, IFN-γ enhanced the recruitment of LC3 onto the parasitophorous vacuole membrane (PVM) and increased the colocalization of lysosomal vesicles with P. vivax compartments. Taken together, these data indicate that IFN-γ mediates the control of liver-stage P. vivax by inducing a noncanonical autophagy pathway resembling that of LC3-associated phagocytosis, in which direct decoration of the PVM with LC3 promotes the fusion of P. vivax compartments with lysosomes and subsequent killing of the pathogen. Understanding the hepatocyte response to IFN-γ during Plasmodium infection and the roles of autophagy-related proteins may provide an urgently needed alternative strategy for the elimination of this human malaria.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.