ArticlePLoS pathogens2010
Leishmania-induced inactivation of the macrophage transcription factor AP-1 is mediated by the parasite metalloprotease GP63.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 147 citations in OpenAlex.
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- Schistosoma japonicum leishmanolysin SjLLPi1 facilitates the invasion of cercariae into the host skin.PLoS pathogens · 2025Article
- Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.PLoS pathogens · 2025Article
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- Comparative characterization of microRNA-71 of Echinococcus granulosus exosomes.Parasite (Paris, France) · 2023Article
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- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- A Novel Role of Secretory Cytosolic Tryparedoxin Peroxidase in Delaying Apoptosis ofMolecular and cellular biology · 2022Article
- Revisiting Leishmania GP63 host cell targets reveals a limited spectrum of substrates.PLoS pathogens · 2022Article
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- Expression Profile of Genes Related to the Th17 Pathway in Macrophages Infected byFrontiers in cellular and infection microbiology · 2022Article
- Three types ofFrontiers in cellular and infection microbiology · 2022Article
- Identification of natural cytochalasins as leads for neglected tropical diseases drug discovery.PloS one · 2022Article
- Isolation, characterization, and functional study of extracellular vesicles derived fromFrontiers in cellular and infection microbiology · 2022Article
- Network-Based Approaches Reveal Potential Therapeutic Targets for Host-Directed Antileishmanial Therapy Driving Drug Repurposing.Microbiology spectrum · 2021Article
- Sandfly Fever Sicilian Virus-Leishmania major co-infection modulates innate inflammatory response favoring myeloid cell infections and skin hyperinflammation.PLoS neglected tropical diseases · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity.
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Registered trials
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.