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Immune Memory–Boosting Dose of Rapamycin Impairs Macrophage Vesicle Acidification and Curtails Glycolysis in Effector CD8 Cells, Impairing Defense against Acute Infections

Goldberg, Emily L, Smithey, Megan J, Lutes, Lydia K, Uhrlaub, Jennifer L, Nikolich-Žugich, Janko·2014·The Journal of Immunology
DOI 10.4049/jimmunol.1400188PMC PMC4119820
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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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Crossref · 10.4049/jimmunol.1400188

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  • In mice, rapamycin is immunomodulatory, improving CD8+ T cell immunological memory while at the same time impairing defenses against acute viral and bacterial infections.

    “In mice, rapamycin has been shown to be immunomodulatory, improving CD8+ T cell immunological memory while at the same time impairing defenses against acute viral and bacterial infections 85.”

    From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [85]

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Research works printed but not linked: 35

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Metadata

Authors
Goldberg, E. L., Smithey, M. J., Lutes, L. K., Uhrlaub, J. L., & Nikolich-Žugich, J.
Affiliations
Department of Immunobiology, University of Arizona College of Medicine , Tucson, AZ 85724
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2014-07
Volume
193
Issue
2
Pages
757-763
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.1400188
PMC
PMC4119820
Cited by
29
References
10
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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