ArticleJournal of innate immunity2015
Redundant and cooperative interactions between TLR5 and NLRC4 in protective lung mucosal immunity against Pseudomonas aeruginosa.
Article in Journal of innate immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting inflammasome, IL-1β, and coagulation in melioidosis.Frontiers in microbiology · 2026Review
- Novel broadly reactive monoclonal antibody protects againstInfection and immunity · 2025Article
- Flagellum-deficientMicrobiology spectrum · 2024Article
- Role of toll-like receptors and nod-like receptors in acute lung infection.Frontiers in immunology · 2023Review
- Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection.European cells & materials · 2021Article
- Review
- UnderstandingCells · 2020Review
- Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.Cold Spring Harbor perspectives in biology · 2020Review
- Mitochondrial Stress Responses and "Mito-Inflammation" in Cystic Fibrosis.Frontiers in pharmacology · 2020Review
- NLRC4 Mutation in flagellin-derived peptide CBLB502 ligand-binding domain reduces the inflammatory response but not radioprotective activity.Journal of radiation research · 2019Article
- HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- NOD-like receptor(s) and host immune responses with Pseudomonas aeruginosa infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Elevated prostaglandin EMucosal immunology · 2018Article
- Emerging Roles of Inflammasomes in Acute Pneumonia.American journal of respiratory and critical care medicine · 2018Review
- Lung epithelial cells: therapeutically inducible effectors of antimicrobial defense.Mucosal immunology · 2018Review
- Interleukin-36γ and IL-36 receptor signaling mediate impaired host immunity and lung injury in cytotoxic Pseudomonas aeruginosa pulmonary infection: Role of prostaglandin E2.PLoS pathogens · 2017Article
- Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors.Clinical and experimental immunology · 2017Article
- IL-24 PromotesJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Article
- IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.Nature communications · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Flagellin is the major structural component of flagella expressed by Pseudomonas aeruginosa (PA) and other bacteria. This protein has been shown to activate the Toll-like receptor TLR5 and the Nod-like receptor Nlrc4/Ipaf, culminating in the expression of innate cytokines and antimicrobial molecules. In this study, we tested the hypothesis that TLR5 and Nlrc4 in combination are required for maximal protective lung innate mucosal immunity against PA. To test this hypothesis, we compared innate immune responses in wild-type (WT) C57B6 mice challenged with PA intratracheally to those observed in mice genetically deficient in TLR5 (TLR5(-/-)) or Nlrc4 (Nlrc4(-/-)) alone or in combination (TLR5/Nlrc4(-/-)). As compared to WT, TLR5(-/-) and Nlrc4(-/-) mice, we observed a significant increase in mortality in TLR5/Nlrc4(-/-) mice, which was associated with a >5,000-fold increase in lung PA colony-forming units and systemic bacterial dissemination. The increased mortality observed in double-deficient mice was not attributable to differences in lung leukocyte influx or lung injury responses. Levels of biologically active IL-1β and IL-18 were reduced in the bronchoalveolar lavage fluid from PA-infected Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, indicating the requirement for Nlrc4-dependent caspase-1 activation. Similarly, decreased production of biologically active IL-1β and activation of caspase-1 was observed in PA-stimulated pulmonary macrophages isolated from Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, whereas the expression of iNOS and the production of NO were significantly reduced in cells from double-mutant but not single-mutant mice. Collectively, our findings indicate that TLR5 and Nlrc4 have both unique and redundant roles in lung antibacterial mucosal immunity, and the absence of both pathogen recognition receptors results in an increase in susceptibility to invasive lung infection.
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