ArticlePLoS pathogens2011
A Yersinia effector with enhanced inhibitory activity on the NF-κB pathway activates the NLRP3/ASC/caspase-1 inflammasome in macrophages.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 94 citations in OpenAlex.
- Yersinia pestis Actively Inhibits the Production of Extracellular Vesicles by Human Neutrophils.Journal of extracellular vesicles · 2025Article
- Raver1 linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pathogenicity and virulence ofVirulence · 2024Review
- Distinct sequential death complexes regulate pyroptosis and IL-1β release in response toScience advances · 2024Article
- Macrophage innate immune responses delineate between defective translocon assemblies produced byVirulence · 2023Article
- Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer.Journal of oncology · 2022Review
- Heightened Virulence ofInfection and immunity · 2021Article
- Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production.Biomolecules · 2021Article
- Characterization, Antioxidant and Anti-Inflammation Capacities of FermentedMolecules (Basel, Switzerland) · 2021Article
- A single-cell atlas of liver metastases of colorectal cancer reveals reprogramming of the tumor microenvironment in response to preoperative chemotherapy.Cell discovery · 2021Article
- Modification of the Pulmonary MyD88 Inflammatory Response Underlies the Role of the Yersinia pestis Pigmentation Locus in Primary Pneumonic Plague.Infection and immunity · 2021Article
- Medroxyprogesterone acetate attenuates demyelination, modulating microglia activation, in a cuprizone neurotoxic demyelinating mouse model.American journal of neurodegenerative disease · 2021Article
- Difference in Strain Pathogenicity of Septicemic Yersinia pestis Infection in a TLR2Infection and immunity · 2020Article
- Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach.Infection and immunity · 2020Article
- Article
- Review
- Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death.Science (New York, N.Y.) · 2018Article
- Necroptosis of infiltrated macrophages drives Yersinia pestis dispersal within buboes.JCI insight · 2018Article
- Constitutive Interferon Maintains GBP Expression Required for Release of Bacterial Components Upstream of Pyroptosis and Anti-DNA Responses.Cell reports · 2018Article
- Evidence that NF-κB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke.Molecular neurobiology · 2018Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJ(KIM)) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJ(KIM) causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJ(KIM) in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJ(KIM) were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJ(CO92), YopJ(KIM) displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJ(KIM) also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJ(CO92), confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways.
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