ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Immune memory-boosting dose of rapamycin impairs macrophage vesicle acidification and curtails glycolysis in effector CD8 cells, impairing defense against acute infections.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Rapamycin not dietary restriction improves resilience against pathogens: a meta-analysis.GeroScience · 2023Pooled it
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Mammalian Target of Rapamycin Complex 1 Activation in Macrophages Contributes to Persistent Lung Inflammation following Respiratory Tract Viral Infection.The American journal of pathology · 2024Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Peripheral tissular analysis of rapamycin's effect as a neuroprotective agent in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Effect of rapamycin on aging and age-related diseases-past and future.GeroScience · 2021Review
- Rapamycin Improves the Response of Effector and Memory CD8Frontiers in cellular and infection microbiology · 2021Article
- Integration of immune-metabolic signals to preserve healthy aging.Translational medicine of aging · 2020Article
- Dietary Intervention Impacts Immune Cell Functions and Dynamics by Inducing Metabolic Rewiring.Frontiers in immunology · 2020Review
- Next Generation Strategies for Geroprotection via mTORC1 Inhibition.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Review
- A novel rapamycin analog is highly selective for mTORC1 in vivo.Nature communications · 2019Article
- The twilight of immunity: emerging concepts in aging of the immune system.Nature immunology · 2018Review
- Rapamycin Does Not Impede Survival or Induction of Antibody Responses to Primary and Heterosubtypic Influenza Infections in Mice.Viral immunology · 2016Article
- Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island.The journals of gerontology. Series A, Biological sciences and medical sciences · 2016Review
- The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging.Cell metabolism · 2016Review
- Preparing for an Aging World: Engaging Biogerontologists, Geriatricians, and the Society.The journals of gerontology. Series A, Biological sciences and medical sciences · 2016Article
- Article
- Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.Aging cell · 2016Article
- mTOR Regulation of Lymphoid Cells in Immunity to Pathogens.Frontiers in immunology · 2016Review
- mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Direct mammalian target of rapamycin (Rapa) complex 1 inhibition by short-term low-dose Rapa treatment has recently been shown to improve CD8 T cell immunological memory. Whereas these studies focused on memory development, the impact of low-dose Rapa on the primary immune response, particularly as it relates to functional effector immunity, is far less clear. In this study, we investigated the impact of acute Rapa treatment on immune effector cell function during the primary immune response to several acute infections. We found that functional CD8 T cell and macrophage responses to both viral and intracellular bacterial pathogens were depressed in mice in vivo and in humans to phorbol ester and calcium ionophore stimulation in vitro in the face of low-dose Rapa treatment. Mechanistically, the CD8 defect was linked to impaired glycolytic switch in stimulated naive cells and the reduced formation of short-lived effector cells. Therefore, more than one cell type required for a protective effector immune response is impaired by Rapa in both mice and humans, at the dose shown to improve immune memory and extend lifespan. This urges caution with regard to the relative therapeutic costs and benefits of Rapa treatment as means to improve immune memory.
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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.