ArticlePLoS pathogens2016
Leishmania major Promastigotes Evade LC3-Associated Phagocytosis through the Action of GP63.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
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- VAPA mediates lipid exchange between Leishmania amazonensis and host macrophages.PLoS pathogens · 2025Article
- Enhanced autophagy and phagocytosis of apoptotic lymphocytes in splenic macrophages of acute ethanol-treated rats: Light and electron microscopic studies.Histology and histopathology · 2024Article
- Molecular Mechanisms of Persistence in Protozoan Parasites.Microorganisms · 2023Review
- Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine.Frontiers in molecular biosciences · 2023Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis.Science advances · 2022Review
- Revisiting Leishmania GP63 host cell targets reveals a limited spectrum of substrates.PLoS pathogens · 2022Article
- VAMP3 and VAMP8 Regulate the Development and Functionality of Parasitophorous Vacuoles Housing Leishmania amazonensis.Infection and immunity · 2022Article
- Transcriptional Shift and Metabolic Adaptations duringMicroorganisms · 2022Article
- Host SUMOylation Pathway Negatively Regulates Protective Immune Responses and PromotesFrontiers in cellular and infection microbiology · 2022Article
- Revisiting the Principles of Designing a Vaccine.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Hide-and-Seek: A Game Played between Parasitic Protists and Their Hosts.Microorganisms · 2021Review
- Protective CD4+ Th1 cell-mediated immunity is reliant upon execution of effector function prior to the establishment of the pathogen niche.PLoS pathogens · 2021Article
- Leishmania donovani Metacyclic Promastigotes Impair Phagosome Properties in Inflammatory Monocytes.Infection and immunity · 2021Article
- Non-canonical autophagy functions of ATG16L1 in epithelial cells limit lethal infection by influenza A virus.The EMBO journal · 2021Article
- Functions of ROS in Macrophages and Antimicrobial Immunity.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
The protozoan Leishmania parasitizes macrophages and evades the microbicidal consequences of phagocytosis through the inhibition of phagolysosome biogenesis. In this study, we investigated the impact of this parasite on LC3-associated phagocytosis, a non-canonical autophagic process that enhances phagosome maturation and functions. We show that whereas internalization of L. major promastigotes by macrophages promoted LC3 lipidation, recruitment of LC3 to phagosomes was inhibited through the action of the parasite surface metalloprotease GP63. Reactive oxygen species generated by the NOX2 NADPH oxidase are necessary for LC3-associated phagocytosis. We found that L. major promastigotes prevented, in a GP63-dependent manner, the recruitment of NOX2 to phagosomes through a mechanism that does not involve NOX2 cleavage. Moreover, we found that the SNARE protein VAMP8, which regulates phagosomal assembly of the NADPH oxidase NOX2, was down-modulated by GP63. In the absence of VAMP8, recruitment of LC3 to phagosomes containing GP63-deficient parasites was inhibited, indicating that VAMP8 is involved in the phagosomal recruitment of LC3. These findings reveal a role for VAMP8 in LC3-associated phagocytosis and highlight a novel mechanism exploited by L. major promastigotes to interfere with the host antimicrobial machinery.
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