ArticleMucosal immunology2021
Epithelium-autonomous NAIP/NLRC4 prevents TNF-driven inflammatory destruction of the gut epithelial barrier in Salmonella-infected mice.
Article in Mucosal immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Comprehensive analyses of pathogen loads and immune responses alongside the gastrointestinal tract upon long-term Salmonella Typhimurium-infection of clinically resistant mice.European journal of microbiology & immunology · 2026Article
- ProbeST: a custom probe design pipeline for dual host-pathogen Spatial Transcriptomics.BMC genomics · 2026Article
- Salmonella Effector SpvC Targets SEC23B of Intestinal Epithelial Cells to Resist Gasdermin D-Mediated Protection Against Systemic Infection.Microorganisms · 2026Article
- Infection strategies ofGut microbes reports · 2026Review
- TTSS-2 virulence drives inflammatory destruction of the gut epithelial barrier and modulates inflammatory response profiles in the Salmonella-infected mouse gut.PLoS pathogens · 2025Article
- Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ.Cell host & microbe · 2025Article
- Determinants of divergentmBio · 2025Article
- The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Enteric tuft cell inflammasome activation drives NKp46+ILC3 IL22 via PGD2 and inhibits Salmonella.The Journal of experimental medicine · 2025Article
- Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.PLoS pathogens · 2025Article
- Mechanisms conferring multi-layered protection against intestinal Salmonella Typhimurium infection.FEMS microbiology reviews · 2025Review
- PANoptosis in Bacterial Infections: A Double-Edged Sword Balancing Host Immunity and Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- Relaxation of mucosal fibronectin fibers in late gut inflammation following neutrophil infiltration in mice.npj biological physics and mechanics · 2025Article
- NLRC4, inflammation and colorectal cancer (Review).International journal of oncology · 2024Review
- The immune interactions of gut glycans and microbiota in health and disease.Molecular microbiology · 2024Review
- Exploring the Immunomodulatory Potential of Human Milk: Aryl Hydrocarbon Receptor Activation and Its Impact on Neonatal Gut Health.Nutrients · 2024Article
- Direct Salmonella injection into enteroid cells allows the study of host-pathogen interactions in the cytosol with high spatiotemporal resolution.PLoS biology · 2024Article
- Non-professional efferocytosis of Salmonella-infected intestinal epithelial cells in the neonatal host.The Journal of experimental medicine · 2024Article
- A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection.Nature communications · 2024Article
- Pyroptosis regulation byFrontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gut epithelium is a critical protective barrier. Its NAIP/NLRC4 inflammasome senses infection by Gram-negative bacteria, including Salmonella Typhimurium (S.Tm) and promotes expulsion of infected enterocytes. During the first ~12-24 h, this reduces mucosal S.Tm loads at the price of moderate enteropathy. It remained unknown how this NAIP/NLRC4-dependent tradeoff would develop during subsequent infection stages. In NAIP/NLRC4-deficient mice, S.Tm elicited severe enteropathy within 72 h, characterized by elevated mucosal TNF (>20 pg/mg) production from bone marrow-derived cells, reduced regeneration, excessive enterocyte loss, and a collapse of the epithelial barrier. TNF-depleting antibodies prevented this destructive pathology. In hosts proficient for epithelial NAIP/NLRC4, a heterogeneous enterocyte death response with both apoptotic and pyroptotic features kept S.Tm loads persistently in check, thereby preventing this dire outcome altogether. Our results demonstrate that immediate and selective removal of infected enterocytes, by locally acting epithelium-autonomous NAIP/NLRC4, is required to avoid a TNF-driven inflammatory hyper-reaction that otherwise destroys the epithelial barrier.
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