ArticlePLoS pathogens2019
Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
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- The Effects of Multiple Maillard Reaction Products in Infant Formula on Host Immunity and Neurotoxicity.Foods (Basel, Switzerland) · 2026Article
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- Effect of Colostrum Components on Early Inflammatory Response, IgG Concentration and Weight Gain in Lambs.Animals : an open access journal from MDPI · 2026Article
- Serum amyloid A in the oral microenvironment: implications for inflammation, host-microbe interactions, and disease monitoring.Frontiers in immunology · 2026Review
- Prediction of influenza virus infection based on deep learning and peripheral blood proteomics: A diagnostic study.Journal of advanced research · 2026Article
- Article
- Serum amyloid A: multifaceted roles in inflammation and cellular interactions.Immunologic research · 2025Review
- Article
- The G-protein coupled receptor OXER1 is a tissue redox sensor essential for intestinal epithelial barrier integrity.bioRxiv : the preprint server for biology · 2025Article
- Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome.bioRxiv : the preprint server for biology · 2024Article
- The Future Exploring of Gut Microbiome-Immunity Interactions: From In Vivo/Vitro Models to In Silico Innovations.Microorganisms · 2024Review
- Associations of Neonatal Dairy Calf Faecal Microbiota with Inflammatory Markers and Future Performance.Animals : an open access journal from MDPI · 2024Article
- Neutrophils: from IBD to the gut microbiota.Nature reviews. Gastroenterology & hepatology · 2024Review
- Modulation of MAPK/NF-κB Pathway and NLRP3 Inflammasome by Secondary Metabolites from Red Algae: A Mechanistic Study.ACS omega · 2023Article
- Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish.Science advances · 2023Article
- Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions.Frontiers in cardiovascular medicine · 2023Review
- Acute-serum amyloid A and A-SAA-derived peptides as formyl peptide receptor (FPR) 2 ligands.Frontiers in endocrinology · 2023Review
- Zebrafish: an efficient vertebrate model for understanding role of gut microbiota.Molecular medicine (Cambridge, Mass.) · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The intestinal microbiota influences the development and function of myeloid lineages such as neutrophils, but the underlying molecular mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one of the most highly induced transcripts in digestive tissues following microbiota colonization. Saa is a conserved secreted protein produced in the intestine and liver with described effects on neutrophils in vitro, however its in vivo functions remain poorly defined. We engineered saa mutant zebrafish to test requirements for Saa on innate immunity in vivo. Zebrafish mutant for saa displayed impaired neutrophil responses to wounding but augmented clearance of pathogenic bacteria. At baseline, saa mutants exhibited moderate neutrophilia and altered neutrophil tissue distribution. Molecular and functional analyses of isolated neutrophils revealed that Saa suppresses expression of pro-inflammatory markers and bactericidal activity. Saa's effects on neutrophils depended on microbiota colonization, suggesting this protein mediates the microbiota's effects on host innate immunity. To test tissue-specific roles of Saa on neutrophil function, we over-expressed saa in the intestine or liver and found that sufficient to partially complement neutrophil phenotypes observed in saa mutants. These results indicate Saa produced by the intestine in response to microbiota serves as a systemic signal to neutrophils to restrict aberrant activation, decreasing inflammatory tone and bacterial killing potential while simultaneously enhancing their ability to migrate to wounds.
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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.