Cited by 165Inflammasome and immune disordersImmune Response and InflammationNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

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Maltez, Vivien I., Tubbs, Alan L., Cook, Kevin D., Aachoui, Youssef, Falcone, E. Liana, Holland, Steven M., Whitmire, Jason K., Miao, Edward A.·2015·Immunity

DOI 10.1016/j.immuni.2015.10.010PMC PMC4654968

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Abstract

Defective neutrophils in patients with chronic granulomatous disease (CGD) cause susceptibility to extracellular and intracellular infections. Microbes must first be ejected from intracellular niches to expose them to neutrophil attack, so we hypothesized that inflammasomes detect certain CGD pathogens upstream of neutrophil killing. Here, we identified one such ubiquitous environmental bacterium, Chromobacterium violaceum, whose extreme virulence was fully counteracted by the NLRC4 inflammasome. Caspase-1 protected via two parallel pathways that eliminated intracellular replication niches. Pyroptosis was the primary bacterial clearance mechanism in the spleen, but both pyroptosis and interleukin-18 (IL-18)-driven natural killer (NK) cell responses were required for liver defense. NK cells cleared hepatocyte replication niches via perforin-dependent cytotoxicity, whereas interferon-γ was not required. These insights suggested a therapeutic approach: exogenous IL-18 restored perforin-dependent cytotoxicity during infection by the inflammasome-evasive bacterium Listeria monocytogenes. Therefore, inflammasomes can trigger complementary programmed cell death mechanisms, directing sterilizing immunity against intracellular bacterial pathogens.

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Authors: Maltez, V. I., Tubbs, A. L., Cook, K. D., Aachoui, Y., Falcone, E. L., Holland, S. M., Whitmire, J. K., & Miao, E. A.
Affiliations: University of North Carolina at Chapel Hill (US)
National Institutes of Health (US)
Corresponding author: Miao, Edward A.
ORCID: Maltez, Vivien I.
Tubbs, Alan L.
Cook, Kevin D.
Aachoui, Youssef
Falcone, E. Liana
Holland, Steven M.
Whitmire, Jason K.
Miao, Edward A.
Venue: Immunity
Publisher: Elsevier BV
Published: 2015-11
Volume: 43
Issue: 5
Pages: 987-997
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2015.10.010
PMC: PMC4654968
OpenAlex: W2111822935
Cited by: 165
References: 50
Citations by year: 2026: 8 · 2025: 6 · 2024: 13 · 2023: 17 · 2022: 30 · 2021: 11 · 2020: 21 · 2019: 13 · 2018: 21 · 2017: 16 · 2016: 9
FWCI: 6.65
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: National Institutes of Health (T32 AI7273-27, AI057141)
National Cancer Institute (P30CA016086)
National Institute of Allergy and Infectious Diseases (T32AI7273-27, R01AI119073, U54AI057141, AI119073, R01AI074862, AI097518-02S1, R56AI110682, T32AI007273, R01AI097518, AI097518, AI057141)
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (P30-CA016086)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: inflammasome, NLRC4 inflammasome, pyroptosis, natural killer cells, NK cell cytotoxicity, perforin, Chromobacterium violaceum, chronic granulomatous disease, caspase-1, IL-18, Listeria monocytogenes, intracellular bacterial pathogens, bacterial clearance, liver infection, spleen, sterilizing immunity
MeSH terms: Pyroptosis, Animals, Bacterial Infections, Calcium-Binding Proteins, Chromobacterium, Granulomatous Disease, Chronic, Interferon-gamma, Killer Cells, Natural, Listeriosis, Listeria monocytogenes, Liver, Mice, Inbred C57BL, Neutrophils, Spleen, Cell Death, Caspase 1, Interleukin-18, Apoptosis Regulatory Proteins, Mice, Inflammasomes

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Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium

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