ArticleBMC infectious diseases2012
Adenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficile infection in mice following vancomycin treatment.
Article in BMC infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Attenuation ofJournal of microbiology and biotechnology · 2026Article
- Damage response signaling by the extracellular adenosine pathway: control of infection outcome during host aging.mSphere · 2025Review
- Clostridioides difficile meets the adenosine system: the art of manipulating host homeostasis.Journal of biomedical science · 2025Review
- ApoE COG 133 mimetic peptide improves survival, infection burden, andExperimental biology and medicine (Maywood, N.J.) · 2025Article
- Reviewing theMicroorganisms · 2024Review
- Effect of Doxycycline in Decreasing the Severity ofAntibiotics (Basel, Switzerland) · 2022Article
- Adenosine receptors differentially mediate enteric glial cell death induced byFrontiers in immunology · 2022Article
- [Advances in the study of the role of adenosine 2A receptor in liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Review
- Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Deletion of the adenosine APurinergic signalling · 2020Article
- Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2.The Journal of experimental medicine · 2020Article
- Butyrate Mitigates Weanling Piglets From Lipopolysaccharide-Induced Colitis by Regulating Microbiota and Energy Metabolism of the Gut-Liver Axis.Frontiers in microbiology · 2020Article
- Protective Effects of Bifidobacterial Strains Against ToxigenicFrontiers in microbiology · 2018Article
- A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection.Infectious diseases and therapy · 2017Review
- Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis.Frontiers in pharmacology · 2016Article
- Review
- Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection.Mucosal immunology · 2015Article
- Danger signal adenosine via adenosine 2a receptor stimulates growth of Porphyromonas gingivalis in primary gingival epithelial cells.Molecular oral microbiology · 2014Article
- Role of leptin-mediated colonic inflammation in defense against Clostridium difficile colitis.Infection and immunity · 2014Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundActivation of the A2A adenosine receptor (A2AAR) decreases production of inflammatory cytokines, prevents C. difficile toxin A-induced enteritis and, in combination with antibiotics, increases survival from sepsis in mice. We investigated whether A2AAR activation improves and A2AAR deletion worsens outcomes in a murine model of C. difficile (strain VPI10463) infection (CDI).
methodsC57BL/6 mice were pretreated with an antibiotic cocktail prior to infection and then treated with vancomycin with or without an A2AAR agonist. A2AAR-/- and littermate wild-type (WT) mice were similarly infected, and IFNγ and TNFα were measured at peak of and recovery from infection.
resultsInfected, untreated mice rapidly lost weight, developed diarrhea, and had mortality rates of 50-60%. Infected mice treated with vancomycin had less weight loss and diarrhea during antibiotic treatment but mortality increased to near 100% after discontinuation of antibiotics. Infected mice treated with both vancomycin and an A2AAR agonist, either ATL370 or ATL1222, had minimal weight loss and better long-term survival than mice treated with vancomycin alone. A2AAR KO mice were more susceptible than WT mice to death from CDI. Increases in cecal IFNγ and blood TNFα were pronounced in the absence of A2AARs.
conclusionIn a murine model of CDI, vancomycin treatment resulted in reduced weight loss and diarrhea during acute infection, but high recurrence and late-onset death, with overall mortality being worse than untreated infected controls. The administration of vancomycin plus an A2AAR agonist reduced inflammation and improved survival rates, suggesting a possible benefit of A2AAR agonists in the management of CDI to prevent recurrent disease.
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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.