CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses

Phillip M. Brailey, Lauren Evans, Juan Carlos López-Rodríguez, Anthony Sinadinos, Victoria Tyrrel, Gavin Kelly, Valerie O’Donnell, Peter Ghazal, Susan John and Patricia Barral ()
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Phillip M. Brailey: King’s College London
Lauren Evans: King’s College London
Juan Carlos López-Rodríguez: King’s College London
Anthony Sinadinos: King’s College London
Victoria Tyrrel: Cardiff University
Gavin Kelly: The Francis Crick Institute
Valerie O’Donnell: Cardiff University
Peter Ghazal: Cardiff University
Susan John: King’s College London
Patricia Barral: King’s College London

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.

Date: 2022
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DOI: 10.1038/s41467-022-34532-x

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