ArticleAmerican journal of respiratory cell and molecular biology2008
Bacterial peptide recognition and immune activation facilitated by human peptide transporter PEPT2.
Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Compositional analysis of bacterial peptidoglycan: insights from peptidoglycomics into structure and function.Journal of bacteriology · 2025Review
- Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.The Journal of membrane biology · 2025Review
- Pattern Recognition by NOD-Like Receptors.Advances in experimental medicine and biology · 2025Review
- Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins.Frontiers in immunology · 2023Review
- Microbiota-derived extracellular vesicles in interkingdom communication in the gut.Journal of extracellular vesicles · 2021Review
- Uptake, recognition and responses to peptidoglycan in the mammalian host.FEMS microbiology reviews · 2021Review
- NOD1 and NOD2 in inflammatory and infectious diseases.Immunological reviews · 2020Review
- Peptidoglycan Muropeptides: Release, Perception, and Functions as Signaling Molecules.Frontiers in microbiology · 2019Review
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Outer Membrane Vesicles From Probiotic and CommensalFrontiers in microbiology · 2018Article
- Clinical Pharmacokinetics and Pharmacodynamics of Colistin.Clinical pharmacokinetics · 2017Review
- LipL21 lipoprotein binding to peptidoglycan enables Leptospira interrogans to escape NOD1 and NOD2 recognition.PLoS pathogens · 2017Article
- Functional Expression of PEPT2 in the Human Distal Lung Epithelial Cell Line NCl-H441.Pharmaceutical research · 2015Article
- Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2015Article
- International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease.Pharmacological reviews · 2015Review
- NOD1 agonist iE-DAP reverses effects of cigarette smoke extract on NOD1 signal pathway in human oral mucosal epithelial cells.International journal of clinical and experimental medicine · 2015Article
- Emerging significance of NLRs in inflammatory bowel disease.Inflammatory bowel diseases · 2014Review
- Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response.Innate immunity · 2014Article
- Recognition of Extracellular Bacteria by NLRs and Its Role in the Development of Adaptive Immunity.Frontiers in immunology · 2013Review
- Functional and molecular expression of the proton-coupled oligopeptide transporters in spleen and macrophages from mouse and human.Molecular pharmaceutics · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Microbial detection requires the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) that are distributed on the cell surface and within the cytosol. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family functions as an intracellular PRR that triggers the innate immune response. The mechanism by which PAMPs enter the cytosol to interact with NLRs, particularly muropeptides derived from the bacterial proteoglycan cell wall, is poorly understood. PEPT2 is a proton-dependent transporter that mediates the active translocation of di- and tripeptides across epithelial tissues, including the lung. Using computational tools, we initially established that bacterial dipeptides, particularly gamma-D-glutamyl-meso-diaminopimelic acid (gamma-iE-DAP), are suitable substrates for PEPT2. We then determined in primary cultures of human upper airway epithelia and transiently transfected CHO-PEPT2 cell lines that gamma-iE-DAP uptake was mediated by PEPT2 with an affinity constant of approximately 193 microM, whereas muramyl dipeptide was not transported. Exposure to gamma-iE-DAP at the apical surface of differentiated, polarized cultures resulted in activation of the innate immune response in an NOD1- and RIP2-dependent manner, resulting in release of IL-6 and IL-8. Based on these findings we report that PEPT2 plays a vital role in microbial recognition by NLR proteins, particularly with regard to airborne pathogens, thereby participating in host defense in the lung.
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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.