ArticlePLoS pathogens2018
NLRP6 negatively regulates pulmonary host defense in Gram-positive bacterial infection through modulating neutrophil recruitment and function.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 100 citations in OpenAlex.
- Aurora A exacerbates antibiotic-resistant Staphylococcus aureus infection through ASC phosphorylation.EMBO reports · 2026Article
- Polymicrobial-driven NLRP6 inflammasome regulates IL-1β production and alveolar bone loss in a murine model of periodontitis.PLoS pathogens · 2026Article
- The challenge of cell death switching in inflammasome-targeted therapies for bacterial and viral infections.Communications biology · 2026Review
- KIAA1199 aggravates sepsis-induced lung injury by promoting complement activation.Communications biology · 2026Article
- NLRC4 deficiency improves host protection during sepsis by regulating macrophage and T-cell responses.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The NLRP6 inflammasome is activated by sterile or pathogen-induced endolysosomal damage.The EMBO journal · 2026Article
- Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026Review
- NKG2A-mediated immune modulation of natural killer cells by Staphylococcus aureus.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Pattern recognition receptors and inflammasome: Now and beyond.Molecules and cells · 2025Review
- Mechanistic insights into the multitarget synergistic efficacy of farrerol and β-lactam antibiotics in combating methicillin-resistantAntimicrobial agents and chemotherapy · 2025Article
- Innate Immunity Never "NODs" Off: NLRs Regulate the Host Anti-Viral Immune Response.Immunological reviews · 2025Review
- PANoptosis in Bacterial Infections: A Double-Edged Sword Balancing Host Immunity and Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- Loss of NLRP6 expression increases the severity of intestinal injury after syngeneic hematopoietic stem cell transplantation.Annals of hematology · 2024Article
- Strategies of bacterial detection by inflammasomes.Cell chemical biology · 2024Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- Article
- A mouse model to distinguish NLRP6-mediated inflammasome-dependent and -independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.Frontiers in cellular and infection microbiology · 2024Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Gram-positive bacteria, including Staphylococcus aureus are endemic in the U.S., which cause life-threatening necrotizing pneumonia. Neutrophils are known to be critical for clearance of S. aureus infection from the lungs and extrapulmonary organs. Therefore, we investigated whether the NLRP6 inflammasome regulates neutrophil-dependent host immunity during pulmonary S. aureus infection. Unlike their wild-type (WT) counterparts, NLRP6 knockout (KO) mice were protected against pulmonary S. aureus infection as evidenced by their higher survival rate and lower bacterial burden in the lungs and extrapulmonary organs. In addition, NLRP6 KO mice displayed increased neutrophil recruitment following infection, and when neutrophils were depleted the protective effect was lost. Furthermore, neutrophils from the KO mice demonstrated enhanced intracellular bacterial killing and increased NADPH oxidase-dependent ROS production. Intriguingly, we found higher NK cell-mediated IFN-γ production in KO mouse lungs, and treatment with IFN-γ was found to enhance the bactericidal ability of WT and KO neutrophils. The NLRP6 KO mice also displayed decreased pyroptosis and necroptosis in the lungs following infection. Blocking of pyroptosis and necroptosis in WT mice resulted in increased survival, reduced bacterial burden in the lungs, and attenuated cytokine production. Taken together, these novel findings show that NLRP6 serves as a negative regulator of neutrophil-mediated host defense during Gram-positive bacterial infection in the lungs through regulating both neutrophil influx and function. These results also suggest that blocking NLRP6 to augment neutrophil-associated bacterial clearance should be considered as a potential therapeutic intervention strategy for treatment of S. aureus pneumonia.
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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.