ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
NLRP1 and NLRP3 inflammasomes are essential for distinct outcomes of decreased cytokines but enhanced bacterial killing upon chronic Nod2 stimulation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- The IL18RAP region disease polymorphism decreases IL-18RAP/IL-18R1/IL-1R1 expression and signaling through innate receptor-initiated pathways.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Metabolic reprogramming, macrophage polarization, and intercellular crosstalk in pelvic inflammatory disease: emerging paradigms and therapeutic opportunities.Frontiers in immunology · 2026Review
- The Role of Pyroptosis-Related Gene Signature and Immune Infiltration in Juvenile Dermatomyositis.Clinical, cosmetic and investigational dermatology · 2025Article
- NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.Frontiers in immunology · 2024Article
- Autophagy in the HTR-8/SVneo Cell Oxidative Stress Model Is Associated with the NLRP1 Inflammasome.Oxidative medicine and cellular longevity · 2021Article
- The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy.Frontiers in cell and developmental biology · 2021Article
- Ubiquitination-Mediated Inflammasome Activation during Bacterial Infection.International journal of molecular sciences · 2019Review
- Peptidoglycan recognition by the innate immune system.Nature reviews. Immunology · 2018Review
- From bacterial killing to immune modulation: Recent insights into the functions of lysozyme.PLoS pathogens · 2017Review
- The NACHT, LRR and PYD Domains-Containing Protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis.Journal of clinical & cellular immunology · 2016Article
- MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional Regulation of IL-8 Production.Journal of innate immunity · 2016Article
- Transcriptome Analysis of HepG2 Cells Expressing ORF3 from Swine Hepatitis E Virus to Determine the Effects of ORF3 on Host Cells.BioMed research international · 2016Article
- Intestinal Antigen-Presenting Cells: Key Regulators of Immune Homeostasis and Inflammation.The American journal of pathology · 2015Review
- Activation of pattern recognition receptors up-regulates metallothioneins, thereby increasing intracellular accumulation of zinc, autophagy, and bacterial clearance by macrophages.Gastroenterology · 2014Article
- NF-κB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms.Molecular and cellular biology · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Upon chronic microbial exposure and pattern-recognition receptor (PRR) stimulation, myeloid-derived cells undergo a distinct transcriptional program relative to acute PRR stimulation, with proinflammatory pathways being downregulated. However, other host-response pathways might be differentially regulated, and this concept has been relatively unexplored. Understanding mechanisms regulating chronic microbial exposure outcomes is important for conditions of ongoing infection or at mucosal surfaces, such as the intestine. The intracellular PRR nucleotide oligomerization domain 2 (Nod2) confers the highest genetic risk toward developing Crohn's disease (CD). We previously identified mechanisms mediating downregulation of proinflammatory pathways upon chronic Nod2 stimulation; here we sought to define how chronic Nod2 stimulation regulates bacterial killing. We find that, despite downregulating cytokine secretion upon restimulation through PRR and live bacteria, chronic Nod2 stimulation of human monocyte-derived macrophages enhances bacterial killing; this dual regulation is absent in CD Nod2-risk carriers. We show that chronic Nod2-mediated reprogramming of human monocyte-derived macrophages to a state of enhanced bacterial killing requires upregulated reactive oxygen/nitrogen species pathway function through increased p67phox/p47phox/nitric oxide synthase-2 expression; selectively knocking down each of these genes reverses the enhanced bacterial killing. Importantly, we find that, during chronic Nod2 stimulation, NLRP3/NLRP1 inflammasome-mediated caspase-1 activation with subsequent IL-1 secretion is essential for the subsequent bifurcation to downregulated proinflammatory cytokines and upregulated bacterial killing. Therefore, we identify mechanisms mediating the distinct inflammatory and microbicidal outcomes upon chronic stimulation of the CD-associated protein Nod2.
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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.