ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Francisella tularensis inhibits the intrinsic and extrinsic pathways to delay constitutive apoptosis and prolong human neutrophil lifespan.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 81 citations in OpenAlex.
- Phagocytosis of Staphylococcus aureus by human neutrophils prevents macrophage efferocytosis and induces programmed necrosis.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
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- Human Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged withInternational journal of molecular sciences · 2024Article
- Microbes and the fate of neutrophils.Immunological reviews · 2023Review
- The emerging oral pathogen, Filifactor alocis, extends the functional lifespan of human neutrophils.Molecular microbiology · 2022Article
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- Metabolic Reprogramming Mediates Delayed Apoptosis of Human Neutrophils Infected WithFrontiers in immunology · 2022Article
- Neutrophil Survival Signaling DuringFrontiers in cellular and infection microbiology · 2022Article
- The Antisocial Network: Cross Talk Between Cell Death Programs in Host Defense.Annual review of immunology · 2021Article
- Review
- Macrophages Demonstrate Guanylate-Binding Protein-Dependent and Bacterial Strain-Dependent Responses toFrontiers in cellular and infection microbiology · 2021Article
- Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation DuringFrontiers in immunology · 2021Article
- Cytosolic Gram-negative bacteria prevent apoptosis by inhibition of effector caspases through lipopolysaccharide.Nature microbiology · 2020Article
- Neutrophils in innate immunity and systems biology-level approaches.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Article
- Manipulation of Autophagy and Apoptosis Facilitates Intracellular Survival ofFrontiers in immunology · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Francisella tularensis is a facultative intracellular bacterium that infects many cell types, including neutrophils. We demonstrated previously that F. tularensis inhibits NADPH oxidase assembly and activity and then escapes the phagosome to the cytosol, but effects on other aspects of neutrophil function are unknown. Neutrophils are short-lived cells that undergo constitutive apoptosis, and phagocytosis typically accelerates this process. We now demonstrate that F. tularensis significantly inhibited neutrophil apoptosis as indicated by morphologic analysis as well as annexin V and TUNEL staining. Thus, ∼80% of infected neutrophils remained viable at 48 h compared with ∼50% of control cells, and ∼40% of neutrophils that ingested opsonized zymosan. In keeping with this finding, processing and activation of procaspases-8, -9, and -3 were markedly diminished and delayed. F. tularensis also significantly impaired apoptosis triggered by Fas crosslinking. Of note, these effects were dose dependent and could be conferred by either intracellular or extracellular live bacteria, but not by formalin-killed organisms or isolated LPS and capsule, and were not affected by disruption of wbtA2 or FTT1236/FTL0708-genes required for LPS O-antigen and capsule biosynthesis. In summary, we demonstrate that F. tularensis profoundly impairs constitutive neutrophil apoptosis via effects on the intrinsic and extrinsic pathways, and thereby define a new aspect of innate immune evasion by this organism. As defects in neutrophil turnover prevent resolution of inflammation, our findings also suggest a mechanism that may in part account for the neutrophil accumulation, granuloma formation, and severe tissue damage that characterizes lethal pneumonic tularemia.
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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.