ArticleAging cell2020
Extracellular adenosine signaling reverses the age-driven decline in the ability of neutrophils to kill Streptococcus pneumoniae.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- From danger to resolution: targeting purinergic signaling in CNS diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Targeting immunosenescence in lung diseases: mechanistic insights and clinical interventions.BMC medicine · 2026Review
- Host Aging Induces a Senescent-Like Phenotype in Neutrophils and Altered Transcriptional Responses to Streptococcus pneumoniae.Aging cell · 2026Article
- Basal activation of ERK1/2 blunts the antimicrobial activity of neutrophils from old hosts against antibody-opsonized Streptococcus pneumoniae.Journal of leukocyte biology · 2026Article
- Extracellular adenosine released by mesenchymal stromal cells from young hosts boosts the antimicrobial activity of neutrophils from aged hosts againstImmunotherapy advances · 2026Article
- Damage response signaling by the extracellular adenosine pathway: control of infection outcome during host aging.mSphere · 2025Review
- Article
- Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses.Journal of leukocyte biology · 2025Article
- Article
- Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems.Ageing research reviews · 2025Review
- Altered CD73-Adenosine Signaling Linked to Infection in Patients undergoing hemodialysis.Journal of inflammation research · 2025Article
- Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response to Streptococcus pneumoniae infection.Immunity & ageing : I & A · 2024Article
- Respiratory Infections in the Aging Lung: Implications for Diagnosis, Therapy, and Prevention.Aging and disease · 2023Review
- Mitochondrial ROS production by neutrophils is required for host antimicrobial function against Streptococcus pneumoniae and is controlled by A2B adenosine receptor signaling.PLoS pathogens · 2022Article
- Age-Related Intestinal Dysbiosis and Enrichment of Gut-specific Bacteria in the Lung Are Associated With Increased Susceptibility toFrontiers in aging · 2022Article
- The Age-Driven Decline in Neutrophil Function Contributes to the Reduced Efficacy of the Pneumococcal Conjugate Vaccine in Old Hosts.Frontiers in cellular and infection microbiology · 2022Article
- Transcriptome Profiling Reveals CD73 and Age-Driven Changes in Neutrophil Responses against Streptococcus pneumoniae.Infection and immunity · 2021Article
- A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity upon Viral Infection and Advanced Age.Infection and immunity · 2021Article
- Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease.Vaccines · 2021Review
- Older but Not Wiser: the Age-Driven Changes in Neutrophil Responses during Pulmonary Infections.Infection and immunity · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The elderly are susceptible to serious infections by Streptococcus pneumoniae (pneumococcus), which calls for a better understanding of the pathways driving the decline in host defense in aging. We previously found that extracellular adenosine (EAD) shaped polymorphonuclear cell (PMN) responses, which are crucial for controlling infection. EAD is produced by CD39 and CD73, and signals via A1, A2A, A2B, and A3 receptors. The objective of this study was to explore the age-driven changes in the EAD pathway and its impact on PMN function. We found in comparison to young mice, PMNs from old mice expressed significantly less CD73, but similar levels of CD39 and adenosine receptors. PMNs from old mice failed to efficiently kill pneumococci ex vivo; however, supplementation with adenosine rescued this defect. Importantly, transfer of PMNs expressing CD73 from young mice reversed the susceptibility of old mice to pneumococcal infection. To identify which adenosine receptor(s) is involved, we used specific agonists and inhibitors. We found that A1 receptor signaling was crucial for PMN function as inhibition or genetic ablation of A1 impaired the ability of PMNs from young mice to kill pneumococci. Importantly, activation of A1 receptors rescued the age-associated defect in PMN function. In exploring mechanisms, we found that PMNs from old mice failed to efficiently kill engulfed pneumococci and that A1 receptor controlled intracellular killing. In summary, targeting the EAD pathway reverses the age-driven decline in PMN antimicrobial function, which has serious implications in combating infections.
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